Synergistic Combination of Luteolin and Asiatic Acid on Cervical Cancer In Vitro and In Vivo
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Cell Culture
2.3. Cell Viability and Drug Combination Assay
2.4. Apoptosis Analysis
2.5. Cell Cycle Analysis
2.6. Mitochondrial ROS Measurement
2.7. Measurement of Glutathione (GSH) and Catalase Levels
2.8. Wound-Healing Assay
2.9. Western Blot Analysis
2.10. Xenograft Mouse Model
2.11. Histopathology and Immunohistochemistry Analyses
2.12. Statistical Analysis
3. Results
3.1. Luteolin and Asiatic Acid Inhibited the Proliferation of Cervical Cancer Cell Lines
3.2. Luteolin and Asiatic Acid Induced Cell Apoptosis in Cervical Cancer Cell Lines
3.3. Luteolin and Asiatic Acid Induced Cell Cycle Arrest in Cervical Cancer Cell Lines
3.4. Luteolin and Asiatic Acid Upregulated Mitochondrial ROS (mitoROS) and Downregulated Glutathione (GSH) in Cervical Cancer Cell Lines
3.5. Luteolin and Asiatic Acid Inhibited Cell Migration of Cervical Cancer Cells
3.6. Luteolin and Asiatic Acid Activated the Mitochondrial-Related Intrinsic Signaling Pathway
3.7. Pro-Apoptotic Mechanism of Luteolin and Asiatic Acid in Cervical Cancer Cells
3.8. Caspase-3-Mediated Intrinsic Apoptosis Pathway Is Involved in Luteolin- and Asiatic Acid-Induced Anti-Proliferation in Cervical Cancer Cells
3.9. Luteolin and Asiatic Acid Suppressed Cervical Cancer Cell-Derived Xenograft Tumors
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLO-BOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef]
- Bethesda. SEER Cancer Stat Facts: Cervical Cancer. National Cancer Institute. Available online: https://seer.cancer.gov/statfacts/html/cervix.html (accessed on 15 April 2022).
- Okunade, K.S. Human papillomavirus and cervical cancer. J. Obstet. Gynaecol. 2020, 40, 602–608. [Google Scholar] [CrossRef]
- de Sanjose, S.; Quint, W.G.V.; Alemany, L.; Geraets, D.T.; Klaustermeier, J.E.; Lloveras, B.; Tous, S.; Felix, A.; Bravo, L.E.; Shin, H.-R.; et al. Human papillomavirus genotype attribution in invasive cervical cancer: A retrospective cross-sectional worldwide study. Lancet Oncol. 2010, 11, 1048–1056. [Google Scholar] [CrossRef]
- Geraets, D.; Alemany, L.; Guimera, N. RIS HPV TT study group. Detection of rare and possibly carcinogenic human papil-lomavirus genotypes as single infections in invasive cervical cancer. J. Pathol. 2012, 228, 534–543. [Google Scholar] [CrossRef] [PubMed]
- Ouyang, L.; Luo, Y.; Tian, M.; Zhang, S.-Y.; Lu, R.; Wang, J.-H.; Kasimu, R.; Li, X. Plant natural products: From traditional compounds to new emerging drugs in cancer therapy. Cell Prolif. 2014, 47, 506–515. [Google Scholar] [CrossRef] [PubMed]
- Aung, T.N.; Qu, Z.; Kortschak, R.D.; Adelson, D.L. Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action. Int. J. Mol. Sci. 2017, 18, 656. [Google Scholar] [CrossRef] [Green Version]
- Kikuchi, H.; Yuan, B.; Hu, X.; Okazaki, M. Chemopreventive and anticancer activity of flavonoids and its possibility for clinical use by combining with conventional chemotherapeutic agents. Am. J. Cancer Res. 2019, 9, 1517–1535. [Google Scholar] [PubMed]
- Lv, J.; Sharma, A.; Zhang, T.; Wu, Y.; Ding, X. Pharmacological review on asiatic acid and its derivatives: A potential com-pound. SLAS Technol. 2018, 23, 111–127. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bunbupha, S.; Pakdeechote, P.; Kukongviriyapan, U.; Prachaney, P.; Kukongviriyapan, V. Asiatic Acid Reduces Blood Pres-sure by Enhancing Nitric Oxide Bioavailability with Modulation of eNOS and p47ᵖʰᵒˣ Expression in l-NAME-induced Hyper-tensive Rats. Phytother. Res. 2014, 28, 1506–1512. [Google Scholar] [CrossRef]
- Jiang, W.; Li, M.; He, F.; Bian, Z.; He, Q.; Wang, X.; Yao, W.; Zhu, L. Neuroprotective effect of asiatic acid against spinal cord injury in rats. Life Sci. 2016, 157, 45–51. [Google Scholar] [CrossRef] [PubMed]
- Jew, S.-S.; Yoo, C.-H.; Lim, D.-Y.; Kim, H.; Mook-Jung, I.; Jung, M.W.; Choi, H.; Jung, Y.-H.; Kim, H.; Park, H.-G. Structure–activity relationship study of asiatic acid derivatives against beta amyloid (Aβ)-induced neurotoxicity. Bioorganic Med. Chem. Lett. 2000, 10, 119–121. [Google Scholar] [CrossRef] [PubMed]
- Ramachandran, V.; Saravanan, R. Glucose uptake through translocation and activation of GLUT4 in PI3K/Akt signaling pathway by asiatic acid in diabetic rats. Hum. Exp. Toxicol. 2015, 34, 884–893. [Google Scholar] [CrossRef] [PubMed]
- Yang, C.; Guo, Y.; Huang, T.-S.; Zhao, J.; Huang, X.-J.; Tang, H.-X.; An, N.; Pan, Q.; Xu, Y.-Z.; Liu, H.-F. Asiatic acid protects against cisplatin-induced acute kidney injury via anti-apoptosis and anti-inflammation. Biomed. Pharmacother. 2018, 107, 1354–1362. [Google Scholar] [CrossRef] [PubMed]
- Lv, H.; Qi, Z.; Wang, S.; Feng, H.; Deng, X.; Ci, X. Asiatic Acid Exhibits Anti-inflammatory and Antioxidant Activities against Lipopolysaccharide and d-Galactosamine-Induced Fulminant Hepatic Failure. Front. Immunol. 2017, 8, 785. [Google Scholar] [CrossRef] [Green Version]
- Liu, W.-H.; Liu, T.-C.; Mong, M.-C. Antibacterial effects and action modes of asiatic acid. Biomed. Pharmacother. 2015, 5, 785. [Google Scholar] [CrossRef] [PubMed]
- Somboonwong, J.; Kankaisre, M.; Tantisira, B.; Tantisira, M.H. Wound healing activities of different extracts of Centella asiatica in incision and burn wound models: An experimental animal study. BMC Complement. Altern. Med. 2012, 12, 103. [Google Scholar] [CrossRef] [Green Version]
- Dong, M.; Zeng, J.; Yang, C.; Qiu, Y.; Wang, X. Asiatic Acid Attenuates Osteoporotic Bone Loss in Ovariectomized Mice Through Inhibiting NF-kappaB/MAPK/Protein Kinase B Signaling Pathway. Front. Pharmacol. 2022, 13, 829741. [Google Scholar] [CrossRef]
- Ren, L.; Cao, Q.-X.; Zhai, F.-R.; Yang, S.-Q.; Zhang, H.-X. Asiatic acid exerts anticancer potential in human ovarian cancer cells via suppression of PI3K/Akt/mTOR signalling. Pharm. Biol. 2016, 54, 2377–2382. [Google Scholar] [CrossRef] [Green Version]
- Wu, T.; Geng, J.; Guo, W.; Gao, J.; Zhu, X. Asiatic acid inhibits lung cancer cell growth in vitro and in vivo by destroying mitochondria. Acta Pharm. Sin. B 2016, 7, 65–72. [Google Scholar] [CrossRef] [Green Version]
- Hao, Y.; Huang, J.; Ma, Y.; Chen, W.; Fan, Q.; Sun, X.; Shao, M.; Cai, H. Asiatic acid inhibits proliferation, migration and induces apoptosis by regulating Pdcd4 via the PI3K/Akt/mTOR/p70S6K signaling pathway in human colon carcinoma cells. Oncol. Lett. 2018, 15, 8223–8230. [Google Scholar] [CrossRef]
- Liu, Y.-T.; Chuang, Y.-C.; Lo, Y.-S.; Lin, C.-C.; Hsi, Y.-T.; Hsieh, M.-J.; Chen, M.-K. Asiatic acid, extracted from Centella asiatica and induces apoptosis pathway through the phosphorylation p38 mitogen-activated protein kinase in cisplatin-resistant na-sopharyngeal carcinoma cells. Biomolecules 2020, 10, 184. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tian, M.; Chen, K.; Huang, J.; Chu, D.; Li, J.; Huang, K.; Ma, C. Asiatic acid inhibits angiogenesis and vascular permeability through the VEGF/VEGFR2 signaling pathway to inhibit the growth and metastasis of breast cancer in mice. Phytotherapy Res. 2021, 35, 6389–6400. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Z.; Cui, L.; Yang, J.; Vong, C.T.; Hu, Y.; Xiao, J.; Chan, G.; He, Z.; Zhong, Z. Anticancer effects of asiatic acid against doxorubicin-resistant breast cancer cells via an AMPK-dependent pathway in vitro. Phytomedicine 2021, 92, 153737. [Google Scholar] [CrossRef] [PubMed]
- Yan, B.; Chen, X.; Liu, J.; Liu, S.; Zhang, J.; Zeng, Q.; Duan, J. Asiatic Acid Induces Mitochondrial Apoptosis via Inhibition of JAK2/STAT3 Signalling Pathway in Human Osteosarcoma. Folia Biol. 2021, 67, 108–117. [Google Scholar]
- Huang, C.-F.; Hung, T.-W.; Yang, S.-F.; Tsai, Y.-L.; Yang, J.-T.; Lin, C.; Hsieh, Y.-H. Asiatic acid from centella asiatica exert anti-invasive ability in human renal cancer cells by modulation of ERK/p38MAPK-mediated MMP15 expression. Phytomedicine 2022, 100, 154036. [Google Scholar] [CrossRef] [PubMed]
- Lian, G.-Y.; Wang, Q.-M.; Tang, P.M.-K.; Zhou, S.; Huang, X.-R.; Lan, H.-Y. Combination of asiatic acid and naringenin modulates NK cell anti-cancer immunity by rebalancing Smad3/Smad7 signaling. Mol. Ther. 2018, 26, 2255–2266. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, J.-F.; Huang, R.-Z.; Yao, G.-Y.; Ye, M.-Y.; Wang, H.-S.; Pan, Y.-M.; Xiao, J.-T. Synthesis and biological evaluation of novel aniline-derived asiatic acid derivatives as potential anticancer agents. Eur. J. Med. Chem. 2014, 86, 175–188. [Google Scholar] [CrossRef]
- Jing, Y.; Wang, G.; Ge, Y.; Xu, M.; Gong, Z. Synthesis, Anti-Tumor and Anti-Angiogenic Activity Evaluations of Asiatic Acid Amino Acid Derivatives. Molecules 2015, 20, 7309–7324. [Google Scholar] [CrossRef] [Green Version]
- Gonçalves, B.M.; Salvador, J.A.; Marín, S.; Cascante, M. Synthesis and anticancer activity of novel fluorinated asiatic acid derivatives. Eur. J. Med. Chem. 2016, 114, 101–117. [Google Scholar] [CrossRef]
- Chen, Z.; Kong, S.; Song, F.; Li, L.; Jiang, H. Pharmacokinetic study of luteolin, apigenin, chrysoeriol and diosmetin after oral administration of Flos Chrysanthemi extract in rats. Fitoterapia 2012, 83, 1616–1622. [Google Scholar] [CrossRef]
- Lim, S.H.; Jung, S.K.; Byun, S.; Lee, E.J.; Hwang, J.A.; Seo, S.G.; Kim, Y.A.; Yu, J.G.; Lee, K.W.; Lee, H.J. Luteolin suppresses UVB-induced photoageing by targeting JNK1 and p90RSK2. J. Cell. Mol. Med. 2013, 17, 672–680. [Google Scholar] [CrossRef] [PubMed]
- Lin, Y.; Shi, R.; Wang, X.; Shen, H.-M. Luteolin, a Flavonoid with Potential for Cancer Prevention and Therapy. Curr. Cancer Drug Targets 2008, 8, 634–646. [Google Scholar] [CrossRef] [PubMed]
- Aziz, N.; Kim, M.-Y.; Cho, J.Y. Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies. J. Ethnopharmacol. 2018, 225, 342–358. [Google Scholar] [CrossRef]
- Seelinger, G.; Merfort, I.; Schempp, C.M. Anti-Oxidant, Anti-Inflammatory and Anti-Allergic Activities of Luteolin. Planta Medica 2008, 74, 1667–1677. [Google Scholar] [CrossRef] [PubMed]
- Cassidy, A.; Minihane, A.M. The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids. Am. J. Clin. Nutr. 2017, 105, 10–22. [Google Scholar] [CrossRef] [Green Version]
- Birt, D.F.; Hendrich, S.; Wang, W. Dietary agents in cancer prevention: Flavonoids and isoflavonoids. Pharmacol. Ther. 2001, 90, 157–177. [Google Scholar] [CrossRef]
- Martin, K.R. Targeting Apoptosis with Dietary Bioactive Agents. Exp. Biol. Med. 2006, 231, 117–129. [Google Scholar] [CrossRef] [Green Version]
- Imran, M.; Rauf, A.; Abu-Izneid, T.; Nadeem, M.; Shariati, M.A.; Khan, I.A.; Imran, A.; Orhan, I.E.; Rizwan, M.; Atif, M. Luteolin, a flavonoid, as an anticancer agent: A review. Biomed. Pharmacother. 2019, 112, 108612. [Google Scholar] [CrossRef]
- Ganai, S.A.; Sheikh, F.A.; Baba, Z.A.; Mir, M.A.; Mantoo, M.A.; Yatoo, M.A. Anticancer activity of the plant flavonoid luteolin against preclinical models of various cancers and insights on different signalling mechanisms modulated. Phytother. Res. 2021, 35, 3509–3532. [Google Scholar] [CrossRef]
- Wu, H.-T.; Lin, J.; Liu, Y.-E.; Chen, H.-F.; Hsu, K.-W.; Lin, S.-H.; Peng, K.-Y.; Lin, K.-J.; Hsieh, C.-C.; Chen, D.-R. Luteolin suppresses androgen receptor-positive triple-negative breast cancer cell proliferation and metastasis by epigenetic regulation of MMP9 expression via the AKT/mTOR signaling pathway. Phytomedicine 2020, 81, 153437. [Google Scholar] [CrossRef]
- Tsai, K.-J.; Tsai, H.-Y.; Tsai, C.-C.; Chen, T.-Y.; Hsieh, T.-H.; Chen, C.-L.; Mbuyisa, L.; Huang, Y.-B.; Lin, M.-W. Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway. Molecules 2021, 26, 6452. [Google Scholar] [CrossRef] [PubMed]
- Potočnjak, I.; Šimić, L.; Gobin, I.; Vukelić, I.; Domitrović, R. Antitumor activity of luteolin in human colon cancer SW620 cells is mediated by the ERK/FOXO3a signaling pathway. Toxicol. Vitr. 2020, 66, 104852. [Google Scholar] [CrossRef] [PubMed]
- Krifa, M.; Alhosin, M.; Muller, C.D.; Gies, J.-P.; Chekir-Ghedira, L.; Ghedira, K.; Mély, Y.; Bronner, C.; Mousli, M. Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16INK4A re-expression related to UHRF1 and DNMT1 down-regulation. J. Exp. Clin. Cancer Res. 2013, 32, 1–10. [Google Scholar] [CrossRef] [Green Version]
- Shi, R.-X.; Ong, C.-N.; Shen, H.-M. Luteolin sensitizes tumor necrosis factor-α-induced apoptosis in human tumor cells. Oncogene 2004, 23, 7712–7721. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Horinaka, M.; Yoshida, T.; Shiraishi, T.; Nakata, S.; Wakada, M.; Nakanishi, R.; Nishino, H.; Sakai, T. The combination of TRAIL and luteolin enhances apoptosis in human cervical cancer HeLa cells. Biochem. Biophys. Res. Commun. 2005, 333, 833–838. [Google Scholar] [CrossRef]
- Chou, T.C.; Talalay, P. Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv. Enzym. Regul. 1984, 22, 27–55. [Google Scholar] [CrossRef]
- Cheng, A.-C.; Huang, T.-C.; Lai, C.-S.; Pan, M.-H. Induction of apoptosis by luteolin through cleavage of Bcl-2 family in human leukemia HL-60 cells. Eur. J. Pharmacol. 2005, 509, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Chiu, F.-L.; Lin, J.-K. Downregulation of androgen receptor expression by luteolin causes inhibition of cell proliferation and induction of apoptosis in human prostate cancer cells and xenografts. Prostate 2007, 68, 61–71. [Google Scholar] [CrossRef]
- Jeon, Y.-W.; Suh, Y.J. Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells. Oncol. Rep. 2012, 29, 819–825. [Google Scholar] [CrossRef] [Green Version]
- Johnson, J.L.; Dia, V.P.; Wallig, M.; de Mejia, E.G. Luteolin and Gemcitabine Protect Against Pancreatic Cancer in an Orthotopic Mouse Model. Pancreas 2015, 44, 144–151. [Google Scholar] [CrossRef] [Green Version]
- Ham, S.; Kim, K.H.; Kwon, T.H.; Bak, Y.; Lee, D.H.; Song, Y.S.; Park, S.-H.; Park, Y.S.; Kim, M.S.; Kang, J.W. Luteolin induces intrinsic apoptosis via inhibition of E6/E7 oncogenes and activation of extrinsic and intrinsic signaling pathways in HPV-18-associated cells. Oncol. Rep. 2014, 31, 2683–2691. [Google Scholar] [CrossRef]
- Kim, Y.-W.; Chaturvedi, P.K.; Chun, S.N.; Lee, Y.G.; Ahn, W.S. Honeybee venom possesses anticancer and antiviral effects by differential inhibition of HPV E6 and E7 expression on cervical cancer cell line. Oncol. Rep. 2015, 33, 1675–1682. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, Q.; Lv, T.; Chen, Y.; Wen, L.; Zhang, J.; Jiang, X.; Liu, F. Apoptosis of HL-60 human leukemia cells induced by Asiatic acid through modulation of B-cell lymphoma 2 family proteins and the mitogen-activated protein kinase signaling pathway. Mol. Med. Rep. 2012, 12, 1429–1434. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Choi, H.-J.; Choi, H.-J.; Chung, T.-W.; Ha, K.-T. Luteolin inhibits recruitment of monocytes and migration of Lewis lung car-cinoma cells by suppressing chemokine (C–C motif) ligand 2 expression in tumor-associated macrophage. Biochem. Biophys. Res. Commun. 2016, 470, 101–106. [Google Scholar] [CrossRef] [PubMed]
- Hsu, Y.-L.; Kuo, P.-L.; Lin, L.-T.; Lin, C.-C. Asiatic Acid, a Triterpene, Induces Apoptosis and Cell Cycle Arrest through Activation of Extracellular Signal-Regulated Kinase and p38 Mitogen-Activated Protein Kinase Pathways in Human Breast Cancer Cells. J. Pharmacol. Exp. Ther. 2004, 313, 333–344. [Google Scholar] [CrossRef] [PubMed]
- Yee, S.B.; Choi, H.J.; Chung, S.W.; Park, D.H.; Sung, B.; Chung, H.Y.; Kim, N.D. Growth inhibition of luteolin on HepG2 cells is induced via p53 and Fas/Fas-ligand besides the TGF-β pathway. Int. J. Oncol. 2015, 47, 747–754. [Google Scholar] [CrossRef] [Green Version]
- Zhang, M.; Wang, R.; Tian, J.; Song, M.; Zhao, R.; Liu, K.; Zhu, F.; Shim, J.H.; Dong, Z.; Lee, M.H. Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo. J. Cell. Mol. Med. 2021, 25, 5560–5571. [Google Scholar] [CrossRef]
- Cai, X.; Ye, T.; Liu, C.; Lu, W.; Lu, M.; Zhang, J.; Wang, M.; Cao, P. Luteolin induced G2 phase cell cycle arrest and apoptosis on non-small cell lung cancer cells. Toxicol. Vitr. 2011, 25, 1385–1391. [Google Scholar] [CrossRef]
- Chen, Z.; Zhang, B.; Gao, F.; Shi, R. Modulation of G2/M cell cycle arrest and apoptosis by luteolin in human colon cancer cells and xenografts. Oncol. Lett. 2018, 15, 1559–1565. [Google Scholar] [CrossRef] [Green Version]
- Song, Y.; Yu, J.; Li, L.; Wang, L.; Dong, L.; Xi, G.; Lu, Y.J.; Li, Z. Luteolin impacts deoxyribonucleic acid repair by modulating the mitogen-activated protein kinase pathway in colorectal cancer. Bioengineered 2022, 13, 10998–11011. [Google Scholar] [CrossRef]
- Ren, L.-Q.; Li, Q.; Zhang, Y. Luteolin Suppresses the Proliferation of Gastric Cancer Cells and Acts in Synergy with Oxaliplatin. BioMed Res. Int. 2020, 2020, 9396512. [Google Scholar] [CrossRef] [PubMed]
- Payen, V.L.; Zampieri, L.X.; Porporato, P.E.; Sonveaux, P. Pro- and antitumor effects of mitochondrial reactive oxygen species. Cancer Metastasis Rev. 2019, 38, 189–203. [Google Scholar] [CrossRef] [Green Version]
- Park, B.C.; Bosire, K.O.; Lee, E.-S.; Lee, Y.S.; Kim, J.-A. Asiatic acid induces apoptosis in SK-MEL-2 human melanoma cells. Cancer Lett. 2005, 218, 81–90. [Google Scholar] [CrossRef] [PubMed]
- Imhoff, B.R.; Hansen, J.M. Extracellular redox status regulates Nrf2 activation through mitochondrial reactive oxygen species. Biochem. J. 2009, 424, 491–500. [Google Scholar] [CrossRef] [PubMed]
- Hwang, J.-T.; Park, O.J.; Lee, Y.K.; Sung, M.J.; Hur, H.J.; Kim, M.S.; Ha, J.H.; Kwon, D.Y. Anti-tumor effect of luteolin is accompanied by AMP-activated protein kinase and nuclear factor-κB modulation in HepG2 hepatocarcinoma cells. Int. J. Mol. Med. 2011, 28, 25–31. [Google Scholar]
- Sato, Y.; Sasaki, N.; Saito, M.; Endo, N.; Kugawa, F.; Ueno, A. Luteolin Attenuates Doxorubicin-Induced Cytotoxicity to MCF-7 Human Breast Cancer Cells. Biol. Pharm. Bull. 2015, 38, 703–709. [Google Scholar] [CrossRef] [Green Version]
- Cheng, W.-Y.; Chiao, M.-T.; Liang, Y.-J.; Yang, Y.-C.; Shen, C.-C.; Yang, C.-Y. Luteolin inhibits migration of human glioblas-toma U-87 MG and T98G cells through downregulation of Cdc42 expression and PI3K/AKT activity. Mol. Biol. Rep. 2013, 40, 5315–5326. [Google Scholar] [CrossRef] [Green Version]
- Chen, K.-C.; Chen, C.-Y.; Lin, C.-J.; Yang, T.-Y.; Chen, T.-H.; Wu, L.-C.; Wu, C.-C. Luteolin attenuates TGF-β1-induced epi-thelial–mesenchymal transition of lung cancer cells by interfering in the PI3K/Akt–NF-κB–Snail pathway. Life Sci. 2013, 93, 924–933. [Google Scholar] [CrossRef]
- Gou, X.-J.; Bai, H.-H.; Liu, L.-W.; Chen, H.-Y.; Shi, Q.; Chang, L.-S.; Ding, M.-M.; Zhou, M.-X.; Chen, W.-L.; Zhang, L.-M. Asiatic Acid Interferes with Invasion and Proliferation of Breast Cancer Cells by Inhibiting WAVE3 Activation through PI3K/AKT Signaling Pathway. BioMed Res. Int. 2020, 2020, 1874387. [Google Scholar] [CrossRef] [Green Version]
- Zhou, Q.; Yan, B.; Hu, X.; Li, X.-B.; Zhang, J.; Fang, J. Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin. Mol. Cancer Ther. 2009, 8, 1684–1691. [Google Scholar] [CrossRef] [Green Version]
- Jeon, Y.W.; Ahn, Y.E.; Chung, W.S.; Choi, H.J.; Suh, Y.J. Synergistic effect between celecoxib and luteolin is dependent on estrogen receptor in human breast cancer cells. Tumor Biol. 2015, 36, 6349–6359. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 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
Chen, Y.-H.; Wu, J.-X.; Yang, S.-F.; Hsiao, Y.-H. Synergistic Combination of Luteolin and Asiatic Acid on Cervical Cancer In Vitro and In Vivo. Cancers 2023, 15, 548. https://doi.org/10.3390/cancers15020548
Chen Y-H, Wu J-X, Yang S-F, Hsiao Y-H. Synergistic Combination of Luteolin and Asiatic Acid on Cervical Cancer In Vitro and In Vivo. Cancers. 2023; 15(2):548. https://doi.org/10.3390/cancers15020548
Chicago/Turabian StyleChen, Ya-Hui, Jyun-Xue Wu, Shun-Fa Yang, and Yi-Hsuan Hsiao. 2023. "Synergistic Combination of Luteolin and Asiatic Acid on Cervical Cancer In Vitro and In Vivo" Cancers 15, no. 2: 548. https://doi.org/10.3390/cancers15020548