Anticancer Activity of Propolis and Its Compounds
Abstract
:1. Introduction
2. Composition of Propolis
3. Mechanisms of Anticancer Activity of Propolis and Its Compounds
3.1. Antiproliferative and Cytotoxic Activities of Propolis and Its Compounds on Cancer Cells
3.2. The Influence of Propolis and Its Compounds on the Apoptotic and Autophagy Process in Cancer Cells
3.3. Propolis and Its Compounds of Anti-Angiogenic Activity
3.4. Anti-Metastatic Activity of Propolis and Its Compounds
4. The Use of Propolis and Its Components in Cancer Therapy
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Iqbal, M.; Fan, T.P.; Watson, D.; Alenezi, S.; Saleh, K.; Sahlan, M. Preliminary studies: The potential anti-angiogenic activities of two Sulawesi Island (Indonesia) propolis and their chemical characterization. Heliyon 2019, 5, e01978. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zabaiou, N.; Fouache, A.; Trousson, A.; Buñay-Noboa, J.; Marceau, G.; Sapin, V.; Zellagui, A.; Baron, S.; Lahouel, M.; Lobaccaro, J.M.A. Ethanolic extract of Algerian propolis decreases androgen receptor transcriptional activity in cultured LNCaP cells. J. Steroid Biochem. Mol. Biol. 2019, 189, 108–115. [Google Scholar] [CrossRef]
- Zabaiou, N.; Fouache, A.; Trousson, A.; Baron, S.; Zellagui, A.; Lahouel, M.; Lobaccaro, J.A. Biological properties of propolis extracts: Something new from an ancient product. Chem. Phys. Lipids 2017, 207, 214–222. [Google Scholar] [CrossRef]
- Santos, L.M.; Fonseca, M.S.; Sokolonski, A.R.; Deegan, K.R.; Araújo, R.P.C.; Umsza-Guez, M.A.; Barbosa, J.D.V.; Portela, R.D.; Machado, B.A.S. Propolis: Types, composition, biological activities, and veterinary product patent prospecting. J. Sci. Food Agric. 2020, 100, 1369–1382. [Google Scholar] [CrossRef]
- Stojanović, S.; Najman, S.J.; Bogdanova-Popov, B.; Najman, S.S. Propolis: Chemical composition, biological and pharmacological activity—A Review. Acta Med. Median. 2020, 59, 108–113. [Google Scholar] [CrossRef]
- Alday, E.; Valencia, D.; Garibay-Escobar, A.; Domínguez-Esquivel, Z.; Piccinelli, A.L.; Rastrelli, L.; Monribot-Villanueva, J.; Guerrero-Analco, J.A.; Robles-Zepeda, R.E.; Hernandez, J.; et al. Plant origin authentication of Sonoran Desert propolis: An antiproliferative propolis from a semi-arid region. Sci. Nat. 2019, 106, 25. [Google Scholar] [CrossRef]
- Catchpole, O.; Mitchell, K.; Bloor, S.; Davis, P.; Suddes, A. Antiproliferative activity of New Zealand propolis and phenolic compounds vs. human colorectal adenocarcinoma cells. Fitoterapia 2015, 106, 167–174. [Google Scholar] [CrossRef] [PubMed]
- Doğan, H.; Silici, S.; Ozcimen, A.A. Biological Effects of Propolis on Cancer. Turk. J. Agric. Food Sci. Technol. 2020, 8, 573. [Google Scholar] [CrossRef] [Green Version]
- Popova, M.; Giannopoulou, E.; Skalicka-Wózniak, K.; Graikou, K.; Widelski, J.; Bankova, V.; Kalofonos, H.; Sivolapenko, G.; Gaweł-Bȩben, K.; Antosiewicz, B.; et al. Characterization and biological evaluation of propolis from Poland. Molecules 2017, 22, 1159. [Google Scholar] [CrossRef]
- Przybyłek, I.; Karpiński, T.M. Antibacterial properties of propolis. Molecules 2019, 24, 2047. [Google Scholar] [CrossRef] [Green Version]
- Martinello, M.; Mutinelli, F. Antioxidant activity in bee products: A review. Antioxidants 2021, 10, 71. [Google Scholar] [CrossRef]
- Ripari, N.; Sartori, A.A.; da Silva Honorio, M.; Conte, F.L.; Tasca, K.I.; Santiago, K.B.; Sforcin, J.M. Propolis antiviral and immunomodulatory activity: A review and perspectives for COVID-19 treatment. J. Pharm. Pharmacol. 2021, 73, 281–299. [Google Scholar] [CrossRef]
- Franchin, M.; Freires, I.A.; Lazarini, J.G.; Nani, B.D.; da Cunha, M.G.; Colón, D.F.; de Alencar, S.M.; Rosalen, P.L. The use of Brazilian propolis for discovery and development of novel anti-inflammatory drugs. Eur. J. Med. Chem. 2018, 153, 49–55. [Google Scholar] [CrossRef]
- de Mendonça, I.C.G.; de Moraes Porto, I.C.C.; do Nascimento, T.G.; de Souza, N.S.; dos Santos Oliveira, J.M.; dos Santos Arruda, R.E.; Mousinho, K.C.; dos Santos, A.F.; Basílio-Júnior, I.D.; Parolia, A.; et al. Brazilian red propolis: Phytochemical screening, antioxidant activity and effect against cancer cells. BMC Complement. Altern. Med. 2015, 15, 357. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Anjum, S.I.; Ullah, A.; Khan, K.A.; Attaullah, M.; Khan, H.; Ali, H.; Bashir, M.A.; Tahir, M.; Ansari, M.J.; Ghramh, H.A.; et al. Composition and functional properties of propolis (bee glue): A review. Saudi J. Biol. Sci. 2019, 26, 1695–1703. [Google Scholar] [CrossRef]
- Zulhendri, F.; Felitti, R.; Fearnley, J.; Ravalia, M. The use of propolis in dentistry, oral health, and medicine: A review. J. Oral Biosci. 2021. [Google Scholar] [CrossRef]
- Kubina, R.; Kabała-Dzik, A.; Dziedzic, A.; Bielec, B.; Wojtyczka, R.D.; Bułdak, R.J.; Wyszyńska, M.; Stawiarska-Pięta, B.; Szaflarska-Stojko, E. The ethanol extract of polish propolis exhibits anti-proliferative and/or pro-apoptotic effect on HCT 116 colon cancer and Me45 Malignant melanoma cells in vitro conditions. Adv. Clin. Exp. Med. 2015, 24, 203–212. [Google Scholar] [CrossRef] [Green Version]
- Kocot, J.; Kiełczykowska, M.; Luchowska-Kocot, D.; Kurzepa, J.; Musik, I. Antioxidant potential of propolis, bee pollen, and royal jelly: Possible medical application. Oxid. Med. Cell. Longev. 2018, 2018. [Google Scholar] [CrossRef]
- Mora, D.P.P.; Santiago, K.B.; Conti, B.J.; de Oliveira Cardoso, E.; Conte, F.L.; Oliveira, L.P.G.; de Assis Golim, M.; Uribe, J.F.C.; Gutiérrez, R.M.; Buitrago, M.R.; et al. The chemical composition and events related to the cytotoxic effects of propolis on osteosarcoma cells: A comparative assessment of Colombian samples. Phyther. Res. 2019, 33, 591–601. [Google Scholar] [CrossRef]
- De Oliveira Reis, J.H.; de Abreu Barreto, G.; Cerqueira, J.C.; dos Anjos, J.P.; Andrade, L.N.; Padilha, F.F.; Druzian, J.I.; MacHado, B.A.S. Evaluation of the antioxidant profile and cytotoxic activity of red propolis extracts from different regions of northeastern Brazil obtained by conventional and ultrasoundassisted extraction. PLoS ONE 2019, 14, e0219063. [Google Scholar] [CrossRef]
- Galeotti, F.; Maccari, F.; Fachini, A.; Volpi, N. Chemical composition and antioxidant activity of propolis prepared in different forms and in different solvents useful for finished products. Foods 2018, 7, 41. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bankova, V.; Bertelli, D.; Borba, R.; Conti, B.J.; Cunha, S.; Danert, C.; Eberlin, M.N.; Falcão, I.; Isla, M.I.; Inés, M.; et al. Standard methods for Apis mellifera propolis research. J. Apic. Res. 2019, 8839, 1–49. [Google Scholar] [CrossRef] [Green Version]
- dos Santos, D.A.; Munari, F.M.; da Silva Frozza, C.O.; Moura, S.; Barcellos, T.; Henriques, J.A.P.; Roesch-Ely, M. Brazilian red propolis extracts: Study of chemical composition by ESI-MS/MS (ESI+) and cytotoxic profiles against colon cancer cell lines. Biotechnol. Res. Innov. 2019, 3, 120–130. [Google Scholar] [CrossRef]
- Noureddine, H.; Hage-Sleiman, R.; Wehbi, B.; Fayyad-Kazan, A.H.; Hayar, S.; Traboulssi, M.; Alyamani, O.A.; Faour, W.H.; ElMakhour, Y. Chemical characterization and cytotoxic activity evaluation of Lebanese propolis. Biomed. Pharmacother. 2017, 95, 298–307. [Google Scholar] [CrossRef]
- Ryu, S.; Lim, W.; Bazer, F.W.; Song, G. Chrysin induces death of prostate cancer cells by inducing ROS and ER stress. J. Cell. Physiol. 2017, 232, 3786–3797. [Google Scholar] [CrossRef] [PubMed]
- Celinska-Janowicz, K.; Zareba, I.; Lazarek, U.; Teul, J.; Tomczyk, M.; Palka, J.; Miltyk, W. Constituents of Propolis: Chrysin, Caffeic Acid, p-Coumaric Acid, and Ferulic Acid Induce PRODH/POX-Dependent Apoptosis in Human Tongue Squamous Cell Carcinoma Cell (CAL-27). Front. Pharmacol. 2018, 9, 336. [Google Scholar] [CrossRef] [Green Version]
- Benguedouar, L.; Lahouel, M.; Gangloff, S.C.; Durlach, A.; Grange, F.; Bernard, P.; Antonicelli, F. Ethanolic extract of Algerian propolis and galangin decreased murine melanoma tumor progression in mice. Anti Cancer Agents Med. Chem. (Former. Curr. Med. Chem. Agents) 2016, 16, 1172–1183. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.X.; Tang, C. Galangin suppresses human laryngeal carcinoma via modulation of caspase-3 and AKT signaling pathways. Oncol. Rep. 2017, 38, 703–714. [Google Scholar] [CrossRef]
- Nguyen, H.X.; Nguyen, M.T.T.; Nguyen, N.T.; Awale, S. Chemical constituents of propolis from Vietnamese Trigona minor and Their antiausterity activity against the PANC-1 human pancreatic cancer cell line. J. Nat. Prod. 2017, 80, 2345–2352. [Google Scholar] [CrossRef]
- Pai, J.T.; Lee, Y.C.; Chen, S.Y.; Leu, Y.L.; Weng, M.S. Propolin C inhibited migration and invasion via suppression of EGFR-mediated epithelial-to-mesenchymal transition in human lung cancer cells. Evid. Based Complement. Altern. Med. 2018, 2018, 7202548. [Google Scholar] [CrossRef] [Green Version]
- Nani, B.D.; Franchin, M.; Lazarini, J.G.; Freires, I.A.; da Cunha, M.G.; Bueno-Silva, B.; de Alencar, S.M.; Murata, R.M.; Rosalen, P.L. Isoflavonoids from Brazilian red propolis down-regulate the expression of cancer-related target proteins: A pharmacogenomic analysis. Phytother. Res. 2018, 32, 750–754. [Google Scholar] [CrossRef] [PubMed]
- Bhargava, P.; Grover, A.; Nigam, N.; Kaul, A.; Doi, M.; Ishida, Y.; Kakuta, H.; Kaul, S.C.; Terao, K.; Wadhwa, R. Anticancer activity of the supercritical extract of Brazilian green propolis and its active component, artepillin C: Bioinformatics and experimental analyses of its mechanisms of action. Int. J. Oncol. 2018, 52, 925–932. [Google Scholar] [CrossRef]
- Arruda, C.; Ribeiro, V.P.; Mejía, J.A.A.; Almeida, M.O.; Goulart, M.O.; Candido, A.C.B.B.; dos Santos, R.A.; Magalhães, L.G.; Martins, C.H.G.; Bastos, J.K. Green propolis: Cytotoxic and leishmanicidal activities of artepillin C, p-Coumaric Acid, and their degradation products. Rev. Bras. Farmacogn. 2020, 30, 169–176. [Google Scholar] [CrossRef]
- Endo, S.; Hoshi, M.; Matsunaga, T.; Inoue, T.; Ichihara, K.; Ikari, A. Autophagy inhibition enhances anticancer efficacy of artepillin C, a cinnamic acid derivative in Brazilian green propolis. Biochem. Biophys. Res. Commun. 2018, 497, 437–443. [Google Scholar] [CrossRef]
- Kabala-Dzik, A.; Rzepecka-Stojko, A.; Kubina, R.; Jastrzebska-Stojko, Z.; Stojko, R.; Wojtyczka, R.D.; Stojko, J. Comparison of Two components of propolis: Caffeic Acid (CA) and Caffeic Acid Phenethyl Ester (CAPE) induce apoptosis and cell cycle arrest of breast cancer cells MDA-MB-231. Molecules 2017, 22, 1554. [Google Scholar] [CrossRef] [Green Version]
- Monteiro Espíndola, K.M.; Ferreira, R.G.; Mosquera Narvaez, L.E.; Rocha Silva Rosario, A.C.; Machado Da Silva, A.H.; Bispo Silva, A.G.; Oliveira Vieira, A.P.; Chagas Monteiro, M. Chemical and pharmacological aspects of caffeic acid and its activity in hepatocarcinoma. Front. Oncol. 2019, 9, 3–5. [Google Scholar] [CrossRef] [Green Version]
- Ren, X.; Liu, J.; Hu, L.; Liu, Q.; Wang, D.; Ning, X. Caffeic acid phenethyl ester inhibits the proliferation of HEp2 cells by regulating Stat3/Plk1 pathway and inducing S phase arrest. Biol. Pharm. Bull. 2019, 42, 1689–1693. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gajek, G.; Marciniak, B.; Lewkowski, J.; Kontek, R. Antagonistic effects of CAPE (a Component of Propolis) on the cytotoxicity and genotoxicity of irinotecan and SN38 in Human gastrointestinal cancer cells in vitro. Molecules 2020, 25, 658. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, H.J.; Shin, J.A.; Yang, I.H.; Won, D.H.; Ahn, C.H.; Kwon, H.J.; Lee, J.S.; Cho, N.P.; Kim, E.C.; Yoon, H.J.; et al. Apoptosis induced by caffeic acid phenethyl ester in human oral cancer cell lines: Involvement of Puma and Bax activation. Arch. Oral Biol. 2017, 84, 94–99. [Google Scholar] [CrossRef]
- Wadhwa, R.; Nigam, N.; Bhargava, P.; Dhanjal, J.K.; Goyal, S.; Grover, A.; Sundar, D.; Ishida, Y.; Terao, K.; Kaul, S.C. Molecular characterization and enhancement of anticancer activity of caffeic acid phenethyl ester by γ cyclodextrin. J. Cancer 2016, 7, 1755–1771. [Google Scholar] [CrossRef] [Green Version]
- Tseng, J.C.; Lin, C.Y.; Su, L.C.; Fu, H.H.; Der Yang, S.; Chuu, C.P. CAPE suppresses migration and invasion of prostate cancer cells via activation of non-canonical Wnt signaling. Oncotarget 2016, 7, 38010–38024. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chung, L.C.; Chiang, K.C.; Feng, T.H.; Chang, K.S.; Chuang, S.T.; Chen, Y.J.; Tsui, K.H.; Lee, J.C.; Juang, H.H. Caffeic acid phenethyl ester upregulates N-myc downstream regulated gene 1 via ERK pathway to inhibit human oral cancer cell growth in vitro and in vivo. Mol. Nutr. Food Res. 2017, 61, 1–30. [Google Scholar] [CrossRef]
- Chiang, K.C.; Yang, S.W.; Chang, K.P.; Feng, T.H.; Chang, K.S.; Tsui, K.H.; Shin, Y.S.; Chen, C.C.; Chao, M.; Juang, H.H. Caffeic acid phenethyl ester induces N-myc downstream regulated gene 1 to inhibit cell proliferation and invasion of human nasopharyngeal cancer cells. Int. J. Mol. Sci. 2018, 19, 1397. [Google Scholar] [CrossRef] [Green Version]
- Fraser, S.P.; Hemsley, F.; Djamgoz, M.B.A. Caffeic acid phenethyl ester: Inhibition of metastatic cell behaviours via voltage-gated sodium channel in human breast cancer in vitro. Int. J. Biochem. Cell Biol. 2016, 71, 111–118. [Google Scholar] [CrossRef]
- Duan, J.; Xiaokaiti, Y.; Fan, S.; Pan, Y.; Li, X.; Li, X. Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells. Oncol. Rep. 2017, 37, 3019–3025. [Google Scholar] [CrossRef] [PubMed]
- Frión-Herrera, Y.; Gabbia, D.; Cuesta-Rubio, O.; De Martin, S.; Carrara, M. Nemorosone inhibits the proliferation and migration of hepatocellular carcinoma cells. Life Sci. 2019, 235, 116817. [Google Scholar] [CrossRef] [PubMed]
- Feitelson, M.A.; Arzumanyan, A.; Kulathinal, R.J.; Blain, S.W.; Holcombe, R.F.; Mahajna, J.; Marino, M.; Martinez-Chantar, M.L.; Nawroth, R.; Sanchez-Garcia, I. Sustained proliferation in cancer: Mechanisms and novel therapeutic targets. In Seminars in Cancer Biology; Elsevier: Amsterdam, The Netherlands, 2015; Volume 35, pp. S25–S54. [Google Scholar]
- Koyunoglu, C. Cancer Cell Growth-A Mini Review Part-1: Proliferation, Nutrient, Warburg Effect. Biochem. Anal. Biochem. 2018, 7. [Google Scholar] [CrossRef]
- Sepúlveda, C.; Núñez, O.; Torres, A.; Guzmán, L.; Wehinger, S. Antitumor Activity of Propolis: Recent Advances in Cellular Perspectives, Animal Models and Possible Applications. Food Rev. Int. 2019, 36, 429–455. [Google Scholar] [CrossRef]
- Hustedt, N.; Durocher, D. The control of DNA repair by the cell cycle. Nat. Cell Biol. 2017, 19, 1–9. [Google Scholar] [CrossRef]
- Hassanpour, S.H.; Dehghani, M. Review of cancer from perspective of molecular. J. Cancer Res. Pract. 2017, 4, 127–129. [Google Scholar] [CrossRef]
- Otto, T.; Sicinski, P. Cell cycle proteins as promising targets in cancer therapy. Nat. Rev. Cancer 2017, 17, 93. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leal-Esteban, L.C.; Fajas, L. Cell cycle regulators in cancer cell metabolism. Biochim. Biophys. Acta BBA Mol. Basis Dis. 2020, 1866, 165715. [Google Scholar] [CrossRef] [PubMed]
- Hu, X.; Eastman, A.E.; Guo, S. Cell cycle dynamics in the reprogramming of cellular identity. FEBS Lett. 2019, 593, 2840–2852. [Google Scholar] [CrossRef]
- Misir, S.; Aliyazicioglu, Y.; Demir, S.; Turan, I.; Hepokur, C. Effect of Turkish Propolis on miRNA Expression, Cell Cycle, and Apoptosis in Human Breast Cancer (MCF-7) Cells. Nutr. Cancer 2020, 72, 133–145. [Google Scholar] [CrossRef] [PubMed]
- Rivero-Cruz, J.F.; Granados-Pineda, J.; Pedraza-Chaverri, J.; Perez-Rojas, J.M.; Kumar-Passari, A.; Diaz-Ruiz, G.; Rivero-Cruz, B.E. Phytochemical Constituents, Antioxidant, Cytotoxic, and Antimicrobial Activities of the Ethanolic Extract of Mexican Brown Propolis. Antioxidants 2020, 9, 70. [Google Scholar] [CrossRef] [Green Version]
- Wezgowiec, J.; Wieczynska, A.; Wieckiewicz, W.; Kulbacka, J.; Saczko, J.; Pachura, N.; Wieckiewicz, M.; Gancarz, R.; Wilk, K.A. Polish Propolis-Chemical Composition and Biological Effects in Tongue Cancer Cells and Macrophages. Molecules 2020, 25, 2426. [Google Scholar] [CrossRef]
- Brihoum, H.; Maiza, M.; Sahali, H.; Boulmeltout, M.; Barratt, G.; Benguedouar, L.; Lahouel, M. Dual effect of Algerian propolis on lung cancer: Antitumor and chemopreventive effects involving antioxidant activity. Braz. J. Pharm. Sci. 2018, 54, 1–12. [Google Scholar] [CrossRef]
- Al-Oudat, B.A.; Alqudah, M.A.; Audat, S.A.; Al-Balas, Q.A.; El-Elimat, T.; Hassan, M.A.; Frhat, I.N.; Azaizeh, M.M. Design, synthesis, and biologic evaluation of novel chrysin derivatives as cytotoxic agents and caspase-3/7 activators. Drug Des. Dev. Ther. 2019, 13, 423–433. [Google Scholar] [CrossRef] [Green Version]
- Bloor, S.; Catchpole, O.; Mitchell, K.; Webby, R.; Davis, P. Antiproliferative Acylated Glycerols from New Zealand Propolis. J. Nat. Prod. 2019, 82, 2359–2367. [Google Scholar] [CrossRef] [PubMed]
- Seyhan, M.F.; Yılmaz, E.; Timirci-Kahraman, Ö.; Saygılı, N.; Kısakesen, H.İ.; Gazioğlu, S.; Gören, A.C.; Eronat, A.P.; Begüm Ceviz, A.; Öztürk, T.; et al. Different propolis samples, phenolic content, and breast cancer cell lines: Variable cytotoxicity ranging from ineffective to potent. IUBMB Life 2019, 71, 619–631. [Google Scholar] [CrossRef]
- Saarem, W.; Wang, F.Y.; Farfel, E. Propolis or caffeic acid phenethyl ester (CAPE) inhibits growth and viability in multiple oral cancer cell lines. Int. J. Med. Biomed. Stud. 2019, 3, 50–55. [Google Scholar] [CrossRef] [Green Version]
- Chiu, H.-F.; Han, Y.-C.; Shen, Y.-C.; Golovinskaia, O.; Venkatakrishnan, K.; Wang, C.-K. Chemopreventive and Chemotherapeutic Effect of Propolis and Its Constituents: A Mini-review. J. Cancer Prev. 2020, 25, 70–78. [Google Scholar] [CrossRef] [PubMed]
- Frión-Herrera, Y.; Gabbia, D.; Scaffidi, M.; Zagni, L.; Cuesta-Rubio, O.; De Martin, S.; Carrara, M. Cuban brown propolis interferes in the crosstalk between colorectal cancer cells and m2 macrophages. Nutrients 2020, 12, 2040. [Google Scholar] [CrossRef]
- Jiang, X.S.; Xie, H.Q.; Li, C.G.; You, M.M.; Zheng, Y.F.; Li, G.Q.; Chen, X.; Zhang, C.P.; Hu, F.L. Chinese Propolis Inhibits the Proliferation of Human Gastric Cancer Cells by Inducing Apoptosis and Cell Cycle Arrest. Evid. Based Complement. Altern. Med. 2020, 2020, 2743058. [Google Scholar] [CrossRef]
- Bailon-Moscoso, N.; Cevallos-Solorzano, G.; Carlos Romero-Benavides, J.; Isabel Ramirez Orellana, M. Natural compounds as modulators of cell cycle arrest: Application for anticancer chemotherapies. Curr. Genom. 2017, 18, 106–131. [Google Scholar] [CrossRef] [Green Version]
- Zingue, S.; Maxeiner, S.; Rutz, J.; Ndinteh, D.T.; Chun, F.K.; Fohouo, F.T.; Njamen, D.; Blaheta, R.A. Ethanol-extracted Cameroonian propolis: Antiproliferative effects and potential mechanism of action in prostate cancer. Andrologia 2020, 52, e13698. [Google Scholar] [CrossRef]
- Hichino, A.; Okamoto, M.; Taga, S.; Akizuki, R.; Endo, S.; Matsunaga, T.; Ikari, A. Down-regulation of claudin-2 expression and proliferation by epigenetic inhibitors in human lung adenocarcinoma A549 cells. J. Biol. Chem. 2017, 292, 2411–2421. [Google Scholar] [CrossRef] [Green Version]
- Ikari, A.; Sato, T.; Watanabe, R.; Yamazaki, Y.; Sugatani, J. Increase in claudin-2 expression by an EGFR/MEK/ERK/c-Fos pathway in lung adenocarcinoma A549 cells. Biochim. Biophys. Acta BBA Mol. Cell Res. 2012, 1823, 1110–1118. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sonoki, H.; Tanimae, A.; Furuta, T.; Endo, S.; Matsunaga, T.; Ichihara, K.; Ikari, A. Caffeic acid phenethyl ester down-regulates claudin-2 expression at the transcriptional and post-translational levels and enhances chemosensitivity to doxorubicin in lung adenocarcinoma A549 cells. J. Nutr. Biochem. 2018, 56, 205–214. [Google Scholar] [CrossRef] [PubMed]
- Aru, B.; Guzelmeric, E.; Akgul, A.; Demirel, G.Y.; Kirmizibekmez, H. Antiproliferative Activity of Chemically Characterized Propolis from Turkey and Its Mechanisms of Action. Chem. Biodivers 2019, 16, e1900189. [Google Scholar] [CrossRef]
- Li, J.; Liu, H.; Liu, X.; Hao, S.; Zhang, Z.; Xuan, H.; Wang, K. Chinese Poplar Propolis Inhibits MDA-MB-231 Cell Proliferation in an Inflammatory Microenvironment by Targeting Enzymes of the Glycolytic Pathway. J. Immunol. Res. 2021, 2021, 1–14. [Google Scholar] [CrossRef]
- Kashani, B.; Zandi, Z.; Pourbagheri-Sigaroodi, A.; Bashash, D.; Ghaffari, S.H. The role of toll-like receptor 4 (TLR4) in cancer progression: A possible therapeutic target? J. Cell. Physiol. 2021, 236, 4121–4137. [Google Scholar] [CrossRef]
- Chang, H.; Wang, Y.; Yin, X.; Liu, X.; Xuan, H. Ethanol extract of propolis and its constituent caffeic acid phenethyl ester inhibit breast cancer cells proliferation in inflammatory microenvironment by inhibiting TLR4 signal pathway and inducing apoptosis and autophagy. BMC Complement. Altern. Med. 2017, 17, 471. [Google Scholar] [CrossRef] [Green Version]
- Kohtz, P.D.; Halpern, A.L.; Eldeiry, M.A.; Hazel, K.; Kalatardi, S.; Ao, L.; Meng, X.; Reece, T.B.; Fullerton, D.A.; Weyant, M.J. Toll-like receptor-4 is a mediator of proliferation in esophageal adenocarcinoma. Ann. Thorac. Surg. 2019, 107, 233–241. [Google Scholar] [CrossRef]
- Nikzad, S.; Baradaran-Ghahfarokhi, M.; Nasri, P. Dose-response modeling using MTT assay: A short review. Life Sci. J. 2014, 11, 432–437. [Google Scholar]
- Adan, A.; Kiraz, Y.; Baran, Y. Cell proliferation and cytotoxicity assays. Curr. Pharm. Biotechnol. 2016, 17, 1213–1221. [Google Scholar] [CrossRef] [PubMed]
- de Carvalho, F.M.A.; Schneider, J.K.; de Jesus, C.V.F.; de Andrade, L.N.; Amaral, R.G.; David, J.M.; Krause, L.C.; Severino, P.; Soares, C.M.F.; Bastos, E.C.; et al. Brazilian Red Propolis: Extracts Production, Physicochemical Characterization, and Cytotoxicity Profile for Antitumor Activity. Biomolecules 2020, 10, 726. [Google Scholar] [CrossRef]
- Botteon, C.E.A.; Silva, L.B.; Ccana-Ccapatinta, G.V.; Silva, T.S.; Ambrosio, S.R.; Veneziani, R.C.S.; Bastos, J.K.; Marcato, P.D. Biosynthesis and characterization of gold nanoparticles using Brazilian red propolis and evaluation of its antimicrobial and anticancer activities. Sci. Rep. 2021, 11, 1974. [Google Scholar] [CrossRef] [PubMed]
- Uçar, M.; Değer, O. Evaluation of cytotoxic and wound healing effect of DMEM extracts of turkish propolis in MDA-MB-231 cell lines. Trop. J. Pharm. Res. 2019, 18, 321–325. [Google Scholar] [CrossRef]
- Turan, I.; Demir, S.; Misir, S.; Kilinc, K.; Mentese, A.; Aliyazicioglu, Y.; Deger, O. Cytotoxic effect of Turkish propolis on liver, colon, breast, cervix and prostate cancer cell lines. Trop. J. Pharm. Res. 2015, 14, 777–782. [Google Scholar] [CrossRef] [Green Version]
- Salem, M.M.; Donia, T.; Abu-Khudir, R.; Ramadan, H.; Ali, E.M.M.; Mohamed, T.M. Propolis potentiates methotrexate anticancer mechanism and reduces its toxic effects. Nutr. Cancer 2020, 72, 460–480. [Google Scholar] [CrossRef]
- Coskun, Z.M.; Ersoz, M.; Gecili, M.; Ozden, A.; Acar, A. Cytotoxic and apoptotic effects of ethanolic propolis extract on C6 glioma cells. Environ. Toxicol. 2020, 35, 768–773. [Google Scholar] [CrossRef] [PubMed]
- Jan, R.; Chaudhry, G.E. Understanding apoptosis and apoptotic pathways targeted cancer therapeutics. Adv. Pharm. Bull. 2019, 9, 205–218. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ichim, G.; Tait, S.W.G. A fate worse than death: Apoptosis as an oncogenic process. Nat. Rev. Cancer 2016, 16, 539. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cao, K.; Tait, S.W.G. Apoptosis and cancer: Force awakens, phantom menace, or both? Int. Rev. Cell Mol. Biol. 2018, 337, 135–152. [Google Scholar] [CrossRef]
- Memmedov, H.; Oktay, L.M.; Durmaz, B.; Günel, N.S.; Yildırım, H.K.; Sözmen, E.Y. Propolis prevents inhibition of apoptosis by potassium bromate in CCD 841 human colon cell. Cell Biochem. Funct. 2020, 38, 510–519. [Google Scholar] [CrossRef] [PubMed]
- Frión-herrera, Y.; Gabbia, D.; Scaffidi, M.; Zagni, L.; Cuesta-rubio, O.; de Martin, S.; Carrara, M. The cuban propolis component nemorosone inhibits proliferation and metastatic properties of human colorectal cancer cells. Int. J. Mol. Sci. 2020, 21, 1827. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Azarshinfam, N.; Tanomand, A.; Soltanzadeh, H.; Rad, F.A. Evaluation of anticancer effects of propolis extract with or without combination with layered double hydroxide nanoparticles on Bcl-2 and Bax genes expression in HT-29 cell lines. Gene Rep. 2021, 23, 101031. [Google Scholar] [CrossRef]
- Elnakady, Y.A.; Rushdi, A.I.; Franke, R.; Abutaha, N.; Ebaid, H.; Baabbad, M.; Omar, M.O.; Al Ghamdi, A.A. Characteristics, chemical compositions and biological activities of propolis from Al-Bahah, Saudi Arabia. Sci. Rep. 2017, 7, 41453. [Google Scholar] [CrossRef] [Green Version]
- Kabała-Dzik, A.; Rzepecka-Stojko, A.; Kubina, R.; Iriti, M.; Wojtyczka, R.D.; Buszman, E.; Stojko, J. Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7—A comparative study. Cell. Mol. Biol. 2018, 64, 1. [Google Scholar] [CrossRef] [Green Version]
- Seydi, E.; Rahimpour, Z.; Salimi, A.; Pourahmad, J. Selective toxicity of chrysin on mitochondria isolated from liver of a HCC rat model. Bioorg. Med. Chem. 2019, 27, 115163. [Google Scholar] [CrossRef] [PubMed]
- Panda, D.; Ray, D.; Behera, D.; Tripathy, D.; Bhanja, D.; Sangeeta, S.; Acharya, D. A Review on Apoptosis: When Death Precedes Life. Eur. J. Mol. Clin. Med. 2020, 7, 1174–1182. [Google Scholar]
- Voss, A.K.; Strasser, A. The essentials of developmental apoptosis. F1000Research 2020, 9. [Google Scholar] [CrossRef]
- Carneiro, B.A.; El-Deiry, W.S. Targeting apoptosis in cancer therapy. Nat. Rev. Clin. Oncol. 2020, 17, 395–417. [Google Scholar] [CrossRef] [PubMed]
- Yue, J.; Lopez, J.M. Understanding MAPK Signaling Pathways in Apoptosis. Int. J. Mol. Sci. 2020, 21, 2346. [Google Scholar] [CrossRef] [Green Version]
- Obeng, E. Apoptosis (programmed cell death) and its signals-A review. Braz. J. Biol. 2021, 81, 1133–1143. [Google Scholar] [CrossRef]
- Shahinozzaman, M.; Basak, B.; Emran, R.; Rozario, P.; Obanda, D. Artepillin C: A comprehensive review of its chemistry, bioavailability, and pharmacological properties. Fitoterapia 2020, 147, 104775. [Google Scholar] [CrossRef] [PubMed]
- Beserra, F.P.; Gushiken, L.F.S.; Hussni, M.F.; Ribeiro, V.P.; Bonamin, F.; Jackson, C.J.; Pellizzon, C.H.; Bastos, J.K. Artepillin C as an outstanding phenolic compound of Brazilian green propolis for disease treatment: A review on pharmacological aspects. Phyther. Res. 2020, 35, 2274–2286. [Google Scholar] [CrossRef]
- Pang, S.; Yee, M.; Saba, Y.; Chino, T. Artepillin C as a targeting survivin molecule in oral squamous cell carcinoma cells in vitro: A preliminary study. J. Oral Pathol. Med. 2018, 47, 48–52. [Google Scholar] [CrossRef] [Green Version]
- Beurel, E.; Jope, R.S. The paradoxical pro-and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways. Prog. Neurobiol. 2006, 79, 173–189. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Das, T.P.; Suman, S.; Alatassi, H.; Ankem, M.K.; Damodaran, C. Inhibition of AKT promotes FOXO3a-dependent apoptosis in prostate cancer. Cell Death Dis. 2016, 7, e2111. [Google Scholar] [CrossRef] [Green Version]
- Naz, S.; Imran, M.; Rauf, A.; Orhan, I.E.; Shariati, M.A.; Iahtisham-Ul-Haq; IqraYasmin; Shahbaz, M.; Qaisrani, T.B.; Shah, Z.A.; et al. Chrysin: Pharmacological and therapeutic properties. Life Sci. 2019, 235, 116797. [Google Scholar] [CrossRef]
- Lim, W.; Ryu, S.; Bazer, F.W.; Kim, S.M.; Song, G. Chrysin attenuates progression of ovarian cancer cells by regulating signaling cascades and mitochondrial dysfunction. J. Cell. Physiol. 2018, 233, 3129–3140. [Google Scholar] [CrossRef]
- Lin, Y.M.; Chen, C.I.; Hsiang, Y.P.; Hsu, Y.C.; Cheng, K.C.; Chien, P.H.; Pan, H.L.; Lu, C.C.; Chen, Y.J. Chrysin attenuates cell viability of human colorectal cancer cells through autophagy induction unlike 5-Fluorouracil/Oxaliplatin. Int. J. Mol. Sci. 2018, 19, 1763. [Google Scholar] [CrossRef] [Green Version]
- Zhang, W.; Lan, Y.; Huang, Q.; Hua, Z. Galangin induces B16F10 melanoma cell apoptosis via mitochondrial pathway and sustained activation of p38 MAPK. Cytotechnology 2013, 65, 447–455. [Google Scholar] [CrossRef] [Green Version]
- Zheng, Y.-Z.; Deng, G.; Liang, Q.; Chen, D.-F.; Guo, R.; Lai, R.-C. Antioxidant activity of quercetin and its glucosides from propolis: A theoretical study. Sci. Rep. 2017, 7, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Frion-Herrera, Y.; Diaz-Garcia, A.; Ruiz-Fuentes, J.; Rodriguez-Sanchez, H.; Mauricio Sforcin, J. Mechanisms underlying the cytotoxic effect of propolis on human laryngeal epidermoid carcinoma cells. Nat. Prod. Res. 2018, 32, 2085–2091. [Google Scholar] [CrossRef]
- Frion-Herrera, Y.; Diaz-Garcia, A.; Ruiz-Fuentes, J.; Rodriguez-Sanchez, H.; Sforcin, J.M. The cytotoxic effects of propolis on breast cancer cells involve PI3K/Akt and ERK1/2 pathways, mitochondrial membrane potential, and reactive oxygen species generation. Inflammopharmacology 2019, 27, 1081–1089. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Saha, S.; Panigrahi, D.P.; Patil, S.; Bhutia, S.K. Autophagy in health and disease: A comprehensive review. Biomed. Pharmacother. 2018, 104, 485–495. [Google Scholar] [CrossRef] [PubMed]
- D’Arcy, M.S. Cell death: A review of the major forms of apoptosis, necrosis and autophagy. Cell Biol. Int. 2019, 43, 582–592. [Google Scholar] [CrossRef] [PubMed]
- Colhado Rodrigues, B.L.; Lallo, M.A.; Perez, E.C. The controversial role of autophagy in tumor development: A systematic review. Immunol. Investig. 2020, 49, 386–396. [Google Scholar] [CrossRef]
- Rajabi, M.; Mousa, S.A. The Role of Angiogenesis in Cancer Treatment. Biomedicines 2017, 5, 34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Teleanu, R.I.; Chircov, C.; Grumezescu, A.M.; Teleanu, D.M. Tumor Angiogenesis and Anti-Angiogenic Strategies for Cancer Treatment. J. Clin. Med. 2019, 9, 84. [Google Scholar] [CrossRef] [Green Version]
- Quintero-Fabian, S.; Arreola, R.; Becerril-Villanueva, E.; Torres-Romero, J.C.; Arana-Argaez, V.; Lara-Riegos, J.; Ramirez-Camacho, M.A.; Alvarez-Sanchez, M.E. Role of Matrix Metalloproteinases in Angiogenesis and Cancer. Front. Oncol. 2019, 9, 1370. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Saman, H.; Raza, S.S.; Uddin, S.; Rasul, K. Inducing Angiogenesis, a Key Step in Cancer Vascularization, and Treatment Approaches. Cancers 2020, 12, 1172. [Google Scholar] [CrossRef]
- Shahinozzaman, M.; Taira, N.; Ishii, T.; Halim, M.A.; Hossain, M.A.; Tawata, S. Anti-Inflammatory, Anti-Diabetic, and Anti-Alzheimer’s Effects of Prenylated Flavonoids from Okinawa Propolis: An Investigation by Experimental and Computational Studies. Molecules 2018, 23, 2479. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takahashi, H.; Nguyen, B.C.Q.; Uto, Y.; Shahinozzaman, M.; Tawata, S.; Maruta, H. 1,2,3-Triazolyl esterization of PAK1-blocking propolis ingredients, artepillin C (ARC) and caffeic acid (CA), for boosting their anti-cancer/anti-PAK1 activities along with cell-permeability. Drug Discov. Ther. 2017, 11, 104–109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fares, J.; Fares, M.Y.; Khachfe, H.H.; Salhab, H.A.; Fares, Y. Molecular principles of metastasis: A hallmark of cancer revisited. Signal Transduct. Target. Ther. 2020, 5. [Google Scholar] [CrossRef] [PubMed]
- Dongre, A.; Weinberg, R.A. New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer. Nat. Rev. Mol. Cell Biol. 2019, 20, 69–84. [Google Scholar] [CrossRef] [PubMed]
- Williams, E.D.; Gao, D.; Redfern, A.; Thompson, E.W. Controversies around epithelial–mesenchymal plasticity in cancer metastasis. Nat. Rev. Cancer 2019, 19, 716–732. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yang, J.; Antin, P.; Berx, G.; Blanpain, C.; Brabletz, T.; Bronner, M.; Campbell, K.; Cano, A.; Casanova, J.; Christofori, G.; et al. Guidelines and definitions for research on epithelial–mesenchymal transition. Nat. Rev. Mol. Cell Biol. 2020, 21, 341–352. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Majidpoor, J.; Mortezaee, K. Steps in metastasis: An updated review. Med. Oncol. 2021, 38, 1–17. [Google Scholar] [CrossRef] [PubMed]
- De Craene, B.; Berx, G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 2013, 13, 97–110. [Google Scholar] [CrossRef] [PubMed]
- Kamdje, A.H.N.; Kamga, P.T.; Simo, R.T.; Vecchio, L.; Etet, P.F.S.; Muller, J.M.; Bassi, G.; Lukong, E.; Goel, R.K.; Amvene, J.M.; et al. Developmental pathways associated with cancer metastasis: Notch, Wnt, and Hedgehog. Cancer Biol. Med. 2017, 14, 109–120. [Google Scholar] [CrossRef] [Green Version]
- Borawska, M.H.; Naliwajko, S.K.; Moskwa, J.; Markiewicz-Zukowska, R.; Puscion-Jakubik, A.; Soroczynska, J. Anti-proliferative and anti-migration effects of Polish propolis combined with Hypericum perforatum L. on glioblastoma multiforme cell line U87MG. BMC Complement. Altern. Med. 2016, 16, 367. [Google Scholar] [CrossRef] [Green Version]
- Bonuccelli, G.; De Francesco, E.M.; de Boer, R.; Tanowitz, H.B.; Lisanti, M.P. NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting “stemness”. Oncotarget 2017, 8, 20667–20678. [Google Scholar] [CrossRef] [Green Version]
- Kabala-Dzik, A.; Rzepecka-Stojko, A.; Kubina, R.; Jastrzebska-Stojko, Z.; Stojko, R.; Wojtyczka, R.D.; Stojko, J. Migration Rate Inhibition of Breast Cancer Cells Treated by Caffeic Acid and Caffeic Acid Phenethyl Ester: An In Vitro Comparison Study. Nutrients 2017, 9, 1144. [Google Scholar] [CrossRef]
- Kabala-Dzik, A.; Rzepecka-Stojko, A.; Kubina, R.; Wojtyczka, R.D.; Buszman, E.; Stojko, J. Caffeic Acid Versus Caffeic Acid Phenethyl Ester in the Treatment of Breast Cancer MCF-7 Cells: Migration Rate Inhibition. Integr. Cancer Ther. 2018, 17, 1247–1259. [Google Scholar] [CrossRef]
- Tan, M.I.; Hayati, I. Inhibition of Mammary Gland Cancer Development by Propolis and Mangostin in Female Mice Balb/C Materials and Methods Tumor Induction in Mice and Treatment by Combination of α-Mangostin and Propolis Extracts. J. Math. Fundam. Sci. 2017, 49, 40–50. [Google Scholar] [CrossRef] [Green Version]
- Schaller, M.D. Cellular functions of FAK kinases: Insight into molecular mechanisms and novel functions. J. Cell Sci. 2010, 123, 1007–1013. [Google Scholar] [CrossRef] [Green Version]
- Jiang, H.; Li, Q.; He, C.; Li, F.; Sheng, H.; Shen, X.; Zhang, X.; Zhu, S.; Chen, H.; Chen, X.; et al. Activation of the Wnt pathway through Wnt2 promotes metastasis in pancreatic cancer. Am. J. Cancer Res. 2014, 4, 537–544. [Google Scholar]
- De Giffoni De Carvalho, J.T.; Da Silva Baldivia, D.; Leite, D.F.; De Araújo, L.C.A.; De Toledo Espindola, P.P.; Antunes, K.A.; Rocha, P.S.; De Picoli Souza, K.; Dos Santos, E.L. Medicinal plants from Brazilian Cerrado: Antioxidant and anticancer potential and protection against chemotherapy toxicity. Oxid. Med. Cell. Longev. 2019, 2019. [Google Scholar] [CrossRef] [Green Version]
- Motawi, T.K.; Abdelazim, S.A.; Darwish, H.A.; Elbaz, E.M.; Shouman, S.A. Modulation of Tamoxifen Cytotoxicity by Caffeic Acid Phenethyl Ester in MCF-7 Breast Cancer Cells. Oxid. Med. Cell. Longev. 2016, 2016. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sameni, H.R.; Yosefi, S.; Alipour, M.; Pakdel, A.; Torabizadeh, N.; Semnani, V.; Bandegi, A.R. Co-administration of 5FU and propolis on AOM/DSS induced colorectal cancer in BALB-c mice. Life Sci. 2021, 276, 119390. [Google Scholar] [CrossRef]
- Wang, C.C.; Wang, Y.X.; Yu, N.Q.; Hu, D.; Wang, X.Y.; Chen, X.G.; Liao, Y.W.; Yao, J.; Wang, H.; He, L.; et al. Brazilian green propolis extract synergizes with protoporphyrin IX-mediated photodynamic therapy via enhancement of intracellular accumulation of protoporphyrin IX and attenuation of NF-κB and COX-2. Molecules 2017, 22, 732. [Google Scholar] [CrossRef] [Green Version]
- Darvishi, N.; Yousefinejad, V.; Akbari, M.E.; Abdi, M.; Moradi, N.; Darvishi, S.; Mehrabi, Y.; Ghaderi, E.; Jamshidi-Naaeini, Y.; Ghaderi, B.; et al. Antioxidant and anti-inflammatory effects of oral propolis in patients with breast cancer treated with chemotherapy: A Randomized controlled trial. J. Herb. Med. 2020, 23, 100385. [Google Scholar] [CrossRef]
- Ebeid, S.A.; Abd El Moneim, N.A.; El-Benhawy, S.A.; Hussain, N.G.; Hussain, M.I. Assessment of the radioprotective effect of propolis in breast cancer patients undergoing radiotherapy. New perspective for an old honey bee product. J. Radiat. Res. Appl. Sci. 2016, 9, 431–440. [Google Scholar] [CrossRef] [Green Version]
- Kuo, C.C.; Wang, R.H.; Wang, H.H.; Li, C.H. Meta-analysis of randomized controlled trials of the efficacy of propolis mouthwash in cancer therapy-induced oral mucositis. Support. Care Cancer 2018, 26, 4001–4009. [Google Scholar] [CrossRef] [PubMed]
- Piredda, M.; Facchinetti, G.; Biagioli, V.; Giannarelli, D.; Armento, G.; Tonini, G.; De Marinis, M.G. Propolis in the prevention of oral mucositis in breast cancer patients receiving adjuvant chemotherapy: A pilot randomised controlled trial. Eur. J. Cancer Care 2017, 26. [Google Scholar] [CrossRef]
- Akhavan-Karbassi, M.H.; Yazdi, M.F.; Ahadian, H.; Sadr-Abad, M.J. Randomized double-blind placebo-controlled trial of propolis for oral mucositis in patients receiving chemotherapy for head and neck cancer. Asian Pac. J. Cancer Prev. 2016, 17, 3611–3614. [Google Scholar]
- Ganesan, M.; Kanimozhi, G.; Pradhapsingh, B.; Khan, H.A.; Alhomida, A.S.; Ekhzaimy, A.; Brindha, G.R.; Prasad, N.R. Phytochemicals reverse P-glycoprotein mediated multidrug resistance via signal transduction pathways. Biomed. Pharmacother. 2021, 139, 111632. [Google Scholar] [CrossRef] [PubMed]
- Mansoori, B.; Mohammadi, A.; Davudian, S.; Shirjang, S.; Baradaran, B. The different mechanisms of cancer drug resistance: A brief review. Adv. Pharm. Bull. 2017, 7, 339–348. [Google Scholar] [CrossRef] [PubMed]
- Sritharan, S.; Sivalingam, N. A comprehensive review on time-tested anticancer drug doxorubicin. Life Sci. 2021, 278, 119527. [Google Scholar] [CrossRef]
- Frión-Herrera, Y.; Gabbia, D.; Díaz-García, A.; Cuesta-Rubio, O.; Carrara, M. Chemosensitizing activity of Cuban propolis and nemorosone in doxorubicin resistant human colon carcinoma cells. Fitoterapia 2019, 136, 104173. [Google Scholar] [CrossRef]
- Kebsa, W.; Lahouel, M.; Rouibah, H.; Zihlif, M.; Ahram, M.; Abu-Irmaileh, B.; Mustafa, E.; Al-Ameer, H.J.; Al Shhab, M. Reversing Multidrug Resistance in Chemo-resistant Human Lung Adenocarcinoma (A549/DOX) Cells by Algerian Propolis Through Direct Inhibiting the P-gp Efflux-pump, G0/G1 Cell Cycle Arrest and Apoptosis Induction. Anticancer Agents Med. Chem. 2018, 18, 1330–1337. [Google Scholar] [CrossRef]
- Banzato, T.P.; Gubiani, J.R.; Bernardi, D.I.; Nogueira, C.R.; Monteiro, A.F.; Juliano, F.F.; De Alencar, S.M.; Pilli, R.A.; De Lima, C.A.D.; Longato, G.B.; et al. Antiproliferative Flavanoid Dimers Isolated from Brazilian Red Propolis. J. Nat. Prod. 2020, 83, 1784–1793. [Google Scholar] [CrossRef]
- Nyman, G.; Oldberg Wagner, S.; Prystupa-Chalkidis, K.; Ryberg, K.; Hagvall, L. Contact allergy in western sweden to propolis of four different origins. Acta Derm. Venereol. 2020, 100, 1–5. [Google Scholar] [CrossRef] [PubMed]
- Toreti, V.C.; Sato, H.H.; Pastore, G.M.; Park, Y.K. Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evid. Based Complement. Altern. Med. 2013, 2013. [Google Scholar] [CrossRef] [PubMed]
Compound Name, IUPAC Name; Concentration Used | Model | Property | Chemical Structure | Reference |
---|---|---|---|---|
Flavonoids, flavanones, flavones and flavonols | ||||
Chrysin (5,7-dihydroxy-2-phenylchromen-4-one) 50 μM 5, 25, 50, 80 µg/mL | DU145 and PC-3 cells CAL-27 cells | induction of apoptosis | | [25,26] |
Galangin (3,5,7-trihydroxy-2-phenylchromen-4-one) 0–40 μM 0–40 μM 10, 20 and 30 mg/kg | mice bearing B16F1 TU212, M4e, HBE, HEP-2 RTE, and HHL-5 cells BALB/c nude mice | induction of apoptosis induction of apoptosis and inhibition of migration | | [27,28] |
Genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one) 0–120 μM | LNCaP cells; mouse BALB/c 3T3 and SVT2 (SV40-transformed BALB/c 3T3) fibroblasts | inhibition of cell cycle | | [3] |
Nymphaeol A/Propolin C ((2S)-2-(3,4-dihydroxyphenyl)-6-[(2E)-3,7-dimethylocta-2,6-dienyl]-5,7-dihydroxy-2,3-dihydrochromen-4-one) 5–20 μM 2.5–20 μM | A549 cells A549 and HCC827 cells | anti-angiogenic activity, inhibition of proliferation inhibition of migration and invasion | | [29,30] |
Nymphaeol C ((2S)-2-[2-[(2E)-3,7-dimethylocta-2,6-dienyl]-3,4-dihydroxyphenyl]-5,7-dihydroxy-6-(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one) 5–20 μM | anti-angiogenic activity, inhibition of proliferation | | [29] | |
Vestitol (3-(2-hydroxy-4-methoxyphenyl)-3,4-dihydro-2H-chromen-7-ol) 0.37, 3.7, 37, and 370 μM | HeLa cells | cytotoxic effect | | [31] |
Aromatic acids and their derivatives | ||||
Artepillin C ((E)-3-[4-hydroxy-3,5-bis(3-methylbut-2-enyl)phenyl]prop-2-enoic acid) 250 μM 100 μg/mL 0–150 μM | HT1080, A549, and U2OS cells BALB/c nude mice AGP-01 and HeLa cells CWR22Rv1 cells | inhibition of proliferation cytotoxic effect autophagy inhibition | | [32,33,34] |
Baccharin ((1R,3S,4S,6R,9R,13S,15R,16S,19R,20E,22Z,26R,27S,28S)-16-hydroxy-19-[(1R)-1-hydroxyethyl]-6,15,27-trimethylspiro [2,5,11,14,18,25-hexaoxahexacyclo [2 4.2.1.03,9.04,6.09,27.013,15]nonacosa-20,22-diene-28,2′-oxirane]-12,24-dione) 0–150 μM | CWR22Rv1 cells | autophagy inhibition | | [34] |
Caffeic acid ((E)-3-(3,4-dihydroxyphenyl)prop-2-enoic acid) 50 and 100 μM 65, 130, 190 µg/mL 30 μg/mL, 200 μg/mL 12.5 μM, 1 mM, 50 μM, 100 mg/kg, 20 mg/kg | MDA-MB-231 cells CAL-27 cells Hep3, SK-Hep1, HepG2 cells | cell cycle arrest in a dose- and time-dependent manner apoptosis activation inhibition of angiogenesis, apoptosis activation | | [26,35,36] |
Caffeic acid phenylethyl ester (2-phenylethyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate) 0.005–0.1 mg/mL 0.5–500 µM 10 mg/kg/day 15 mg/kg | AGS, HCT116, HT29, YD15, HSC-4, HN22, MCF-17, MDA-MB-231, MDA-MB-468, A549, HT1080, G361, U2OS, LNCaP, PC-3, DU145, Hep2, SAS, OECM-1, TW01, TW04, SW620, H460 and PANC-1 cells Balb/c nude mice BALB/c AnM-Foxn-1 mice | inhibition of proliferation, migration and invasion, pro-apoptotic activity anti-metastatic activity | | [3,35,37,38,39,40,41,42,43,44,45] |
Ferulic acid ((E)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoic acid) 50, 100, 150 µg/mL | CAL-27 cells | apoptosis activation | | [26] |
p-coumaric acid ((E)-3-(4-hydroxyphenyl)prop-2-enoic acid) 100 μg/mL 70, 140, 210 µg/mL | AGP-01 and HeLa cells CAL-27 cells | cytotoxic effect apoptosis activation | | [26,33] |
Other | ||||
Frondoside A (sodium;[(3R,4R,5R,6S)-6-[(2S,4S,6S,12R,13R,18R)-4-acetyloxy-2,6,13,17,17-pentamethyl-6-(4-methylpentyl)-8-oxo-7-oxapentacyclo[10.8.0.02,9.05,9.013,18]icos-1(20)-en-16-yl]oxy]-5-[(2S,3R,4S,5S,6R)-5-[(2S,3R,4S,5R)-4-[(2S,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-methoxyoxan-2-yl]oxy-3,5-dihydroxyoxan-2-yl]oxy-4-hydroxy-6-methyl-3-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxyoxan-2-yl]oxy-4-hydroxyoxan-3-yl] sulfate) 0.3–1.2 μM | A549 cells | anti-angiogenic activity, inhibition of proliferation | | [29] |
Nemorosone ((1R,5R,7S)-1-benzoyl-4-hydroxy-8,8-dimethyl-3,5,7-tris(3-methylbut-2-enyl)bicyclo[3.3.1]non-3-ene-2,9-dione) 5–50 μM | HT-29 and THP-1 cells | inhibition of migration and proliferation | | [46] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Forma, E.; Bryś, M. Anticancer Activity of Propolis and Its Compounds. Nutrients 2021, 13, 2594. https://doi.org/10.3390/nu13082594
Forma E, Bryś M. Anticancer Activity of Propolis and Its Compounds. Nutrients. 2021; 13(8):2594. https://doi.org/10.3390/nu13082594
Chicago/Turabian StyleForma, Ewa, and Magdalena Bryś. 2021. "Anticancer Activity of Propolis and Its Compounds" Nutrients 13, no. 8: 2594. https://doi.org/10.3390/nu13082594
APA StyleForma, E., & Bryś, M. (2021). Anticancer Activity of Propolis and Its Compounds. Nutrients, 13(8), 2594. https://doi.org/10.3390/nu13082594