Synergistic Anti-Cancer Effects of Curcumin and Thymoquinone Against Melanoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Alamar Blue Viability Assay
2.3. Multicellular Tumor Spheroid Culture (MCTS) and Imaging
2.4. Viability Measurement in Spheroids
2.5. Apoptosis Assay
2.6. Measurement of Intracellular ROS Generation
2.7. Caspase Activity Assay
2.8. LC-MS Metabolomic Analysis
2.9. Isolation of Nucleic Acids and Next-Generation Sequencing (NGS)
2.10. Differential Expression Analysis
2.11. Quantitative Real-Time Polymerase Chain Reaction (RT-PCR)
2.12. Statistical Analysis
3. Results and Discussion
3.1. Curcumin and Thymoquinone Synergistically Inhibited Cell Viability in A375 Melanoma Cancer Cells
3.2. Curcumin and Thymoquinone Synergistically Inhibited Cell Viability in A375 Melanoma Cancer Cells in the Spheroid Model
3.3. Curcumin and Thymoquinone Induce Oxidative Stress in A375 Cells Using the Mitochondrial Pathway
3.4. TQ and CU Regulate Differentially Expressed Genes (DEGs)
3.5. TQ and CU Drive Cellular Metabolomic Rewiring
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
- Saginala, K.; Barsouk, A.; Aluru, J.S.; Rawla, P.; Barsouk, A. Epidemiology of Melanoma. Med. Sci. 2021, 9, 63. [Google Scholar] [CrossRef] [PubMed]
- Miller, A.J.; Mihm, M.C., Jr. Melanoma. N. Engl. J. Med. 2006, 355, 51–65. [Google Scholar] [CrossRef] [PubMed]
- Shain, A.H.; Bastian, B.C. From melanocytes to melanomas. Nat. Rev. Cancer 2016, 16, 345–358. [Google Scholar] [CrossRef] [PubMed]
- Longley, D.B.; Johnston, P.G. Molecular mechanisms of drug resistance. J. Pathol. 2005, 205, 275–292. [Google Scholar] [CrossRef]
- Ravindranathan, P.; Pasham, D.; Balaji, U.; Cardenas, J.; Gu, J.; Toden, S.; Goel, A. A combination of curcumin and oligomeric proanthocyanidins offer superior anti-tumorigenic properties in colorectal cancer. Sci. Rep. 2018, 8, 13869. [Google Scholar] [CrossRef]
- Jin, H.; Wang, L.; Bernards, R. Rational combinations of targeted cancer therapies: Background, advances and challenges. Nat. Rev. Drug Discov. 2023, 22, 213–234. [Google Scholar] [CrossRef]
- DiMarco-Crook, C.; Rakariyatham, K.; Li, Z.; Du, Z.; Zheng, J.; Wu, X.; Xiao, H. Synergistic anticancer effects of curcumin and 3′,4′-didemethylnobiletin in combination on colon cancer cells. J. Food Sci. 2020, 85, 1292–1301. [Google Scholar] [CrossRef]
- Rahman, M.A.; Hannan, M.A.; Dash, R.; Rahman, M.H.; Islam, R.; Uddin, M.J.; Sohag, A.A.; Rahman, M.H.; Rhim, H. Phytochemicals as a Complement to Cancer Chemotherapy: Pharmacological Modulation of the Autophagy-Apoptosis Pathway. Front. Pharmacol. 2021, 12, 639628. [Google Scholar] [CrossRef]
- Neutel, J.M. The use of combination drug therapy in the treatment of hypertension. Prog. Cardiovasc. Nurs. 2002, 17, 81–88. [Google Scholar] [CrossRef]
- Shimura, T.; Sharma, P.; Sharma, G.G.; Banwait, J.K.; Goel, A. Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer. Sci. Rep. 2021, 11, 7548. [Google Scholar] [CrossRef]
- Ekor, M. The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front. Pharmacol. 2014, 4, 177. [Google Scholar] [CrossRef] [PubMed]
- Yun, J.H.; Park, Y.G.; Lee, K.M.; Kim, J.; Nho, C.W. Curcumin induces apoptotic cell death via Oct4 inhibition and GSK-3β activation in NCCIT cells. Mol. Nutr. Food Res. 2015, 59, 1053–1062. [Google Scholar] [CrossRef] [PubMed]
- Farghadani, R.; Naidu, R. Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer. Cancers 2021, 13, 3427. [Google Scholar] [CrossRef] [PubMed]
- Hosseini, S.M.; Taghiabadi, E.; Abnous, K.; Hariri, A.T.; Pourbakhsh, H.; Hosseinzadeh, H. Protective effect of thymoquinone, the active constituent of Nigella sativa fixed oil, against ethanol toxicity in rats. Iran. J. Basic. Med. Sci. 2017, 20, 927–939. [Google Scholar] [CrossRef] [PubMed]
- Raut, P.K.; Lee, H.S.; Joo, S.H.; Chun, K.S. Thymoquinone induces oxidative stress-mediated apoptosis through downregulation of Jak2/STAT3 signaling pathway in human melanoma cells. Food Chem. Toxicol. 2021, 157, 112604. [Google Scholar] [CrossRef]
- Ahmad, I.; Muneer, K.M.; Tamimi, I.A.; Chang, M.E.; Ata, M.O.; Yusuf, N. Thymoquinone suppresses metastasis of melanoma cells by inhibition of NLRP3 inflammasome. Toxicol. Appl. Pharmacol. 2013, 270, 70–76. [Google Scholar] [CrossRef]
- Li, S.; Wu, R.; Wang, L.; Dina Kuo, H.C.; Sargsyan, D.; Zheng, X.; Wang, Y.; Su, X.; Kong, A.N. Triterpenoid ursolic acid drives metabolic rewiring and epigenetic reprogramming in treatment/prevention of human prostate cancer. Mol. Carcinog. 2022, 61, 111–121. [Google Scholar] [CrossRef]
- Shannar, A.; Sarwar, M.S.; Dave, P.D.; Chou, P.J.; Peter, R.M.; Xu, J.; Pan, Y.; Rossi, F.; Kong, A.N. Cyproheptadine inhibits in vitro and in vivo lung metastasis and drives metabolic rewiring. Mol. Biol. Rep. 2024, 51, 1139. [Google Scholar] [CrossRef]
- Guo, Y.; Su, Z.Y.; Zhang, C.; Gaspar, J.M.; Wang, R.; Hart, R.P.; Verzi, M.P.; Kong, A.N. Mechanisms of colitis-accelerated colon carcinogenesis and its prevention with the combination of aspirin and curcumin: Transcriptomic analysis using RNA-seq. Biochem. Pharmacol. 2017, 135, 22–34. [Google Scholar] [CrossRef]
- El-Far, A.H.; Saddiq, A.A.; Mohamed, S.A.; Almaghrabi, O.A.; Mousa, S.A. Curcumin and Thymoquinone Combination Attenuates Breast Cancer Cell Lines’ Progression. Integr. Cancer Ther. 2022, 21, 15347354221099537. [Google Scholar] [CrossRef]
- Zhang, Y.P.; Li, Y.Q.; Lv, Y.T.; Wang, J.M. Effect of curcumin on the proliferation, apoptosis, migration, and invasion of human melanoma A375 cells. Genet. Mol. Res. 2015, 14, 1056–1067. [Google Scholar] [CrossRef] [PubMed]
- Liao, W.; Xiang, W.; Wang, F.F.; Wang, R.; Ding, Y. Curcumin inhibited growth of human melanoma A375 cells via inciting oxidative stress. Biomed. Pharmacother. 2017, 95, 1177–1186. [Google Scholar] [CrossRef] [PubMed]
- Szlasa, W.; Supplitt, S.; Drąg-Zalesińska, M.; Przystupski, D.; Kotowski, K.; Szewczyk, A.; Kasperkiewicz, P.; Saczko, J.; Kulbacka, J. Effects of curcumin based PDT on the viability and the organization of actin in melanotic (A375) and amelanotic melanoma (C32)-in vitro studies. Biomed. Pharmacother. 2020, 132, 110883. [Google Scholar] [CrossRef] [PubMed]
- El-Najjar, N.; Chatila, M.; Moukadem, H.; Vuorela, H.; Ocker, M.; Gandesiri, M.; Schneider-Stock, R.; Gali-Muhtasib, H. Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling. Apoptosis 2010, 15, 183–195. [Google Scholar] [CrossRef] [PubMed]
- Park, J.E.; Kim, D.H.; Ha, E.; Choi, S.M.; Choi, J.S.; Chun, K.S.; Joo, S.H. Thymoquinone induces apoptosis of human epidermoid carcinoma A431 cells through ROS-mediated suppression of STAT3. Chem. Biol. Interact. 2019, 312, 108799. [Google Scholar] [CrossRef]
- Kapałczyńska, M.; Kolenda, T.; Przybyła, W.; Zajączkowska, M.; Teresiak, A.; Filas, V.; Ibbs, M.; Bliźniak, R.; Łuczewski, Ł.; Lamperska, K. 2D and 3D cell cultures-a comparison of different types of cancer cell cultures. Arch. Med. Sci. 2018, 14, 910–919. [Google Scholar] [CrossRef]
- Mitrakas, A.G.; Tsolou, A.; Didaskalou, S.; Karkaletsou, L.; Efstathiou, C.; Eftalitsidis, E.; Marmanis, K.; Koffa, M. Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis. Int. J. Mol. Sci. 2023, 24, 6949. [Google Scholar] [CrossRef]
- Pavlović, M.; Nikolić, S.; Gligorijević, N.; Dojčinović, B.; Aranđelović, S.; Grgurić-Šipka, S.; Radulović, S. New organoruthenium compounds with pyrido[2′,3′:5,6]pyrazino[2,3-f][1, 10]phenanthroline: Synthesis, characterization, cytotoxicity, and investigation of mechanism of action. J. Biol. Inorg. Chem. 2019, 24, 297–310. [Google Scholar] [CrossRef]
- Sirenko, O.; Mitlo, T.; Hesley, J.; Luke, S.; Owens, W.; Cromwell, E.F. High-content assays for characterizing the viability and morphology of 3D cancer spheroid cultures. Assay Drug Dev. Technol. 2015, 13, 402–414. [Google Scholar] [CrossRef]
- Zorov, D.B.; Juhaszova, M.; Sollott, S.J. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol. Rev. 2014, 94, 909–950. [Google Scholar] [CrossRef]
- Handy, D.E.; Loscalzo, J. Redox regulation of mitochondrial function. Antioxid. Redox Signal 2012, 16, 1323–1367. [Google Scholar] [CrossRef] [PubMed]
- Tummers, B.; Green, D.R. Caspase-8: Regulating life and death. Immunol. Rev. 2017, 277, 76–89. [Google Scholar] [CrossRef] [PubMed]
- Li, P.; Zhou, L.; Zhao, T.; Liu, X.; Zhang, P.; Liu, Y.; Zheng, X.; Li, Q. Caspase-9: Structure, mechanisms and clinical application. Oncotarget 2017, 8, 23996–24008. [Google Scholar] [CrossRef] [PubMed]
- Mustika, R.; Budiyanto, A.; Nishigori, C.; Ichihashi, M.; Ueda, M. Decreased expression of Apaf-1 with progression of melanoma. Pigment. Cell Res. 2005, 18, 59–62. [Google Scholar] [CrossRef]
- Ashour, A.E.; Ahmed, A.F.; Kumar, A.; Zoheir, K.M.A.; Aboul-Soud, M.A.; Ahmad, S.F.; Attia, S.M.; Abd-Allah, A.R.A.; Cheryan, V.T.; Rishi, A.K. Thymoquinone inhibits growth of human medulloblastoma cells by inducing oxidative stress and caspase-dependent apoptosis while suppressing NF-κB signaling and IL-8 expression. Mol. Cell. Biochem. 2016, 416, 141–155. [Google Scholar] [CrossRef]
- Ullah, R.; Rehman, A.; Zafeer, M.F.; Rehman, L.; Khan, Y.A.; Khan, M.A.; Khan, S.N.; Khan, A.U.; Abidi, S.M. Anthelmintic Potential of Thymoquinone and Curcumin on Fasciola gigantica. PLoS ONE 2017, 12, e0171267. [Google Scholar] [CrossRef]
- Marnett, L.J. Oxyradicals and DNA damage. Carcinogenesis 2000, 21, 361–370. [Google Scholar] [CrossRef]
- Nakamura, H.; Takada, K. Reactive oxygen species in cancer: Current findings and future directions. Cancer Sci. 2021, 112, 3945–3952. [Google Scholar] [CrossRef]
- Arfin, S.; Jha, N.K.; Jha, S.K.; Kesari, K.K.; Ruokolainen, J.; Roychoudhury, S.; Rathi, B.; Kumar, D. Oxidative Stress in Cancer Cell Metabolism. Antioxidants 2021, 10, 642. [Google Scholar] [CrossRef]
- Ma, D.; Pignanelli, C.; Tarade, D.; Gilbert, T.; Noel, M.; Mansour, F.; Adams, S.; Dowhayko, A.; Stokes, K.; Vshyvenko, S.; et al. Cancer Cell Mitochondria Targeting by Pancratistatin Analogs is Dependent on Functional Complex II and III. Sci. Rep. 2017, 7, 42957. [Google Scholar] [CrossRef]
- Diki, D.; Dwisatyadini, M. Curcumin Affecting Caspase 1 and Caspase 9 Increase and Cell Death in Cervical Cancer Cell Culture. In Proceedings of the The 3rd KOBI Congress, International and National Conferences, Bengkulu, Indonesia, 24–25 November 2020. [Google Scholar]
- Huang, C.; Lu, H.-F.; Chen, Y.-H.; Chen, J.-C.; Chou, W.-H.; Huang, H.-C. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and –independent apoptosis via Smad or Akt signaling pathways in HOS cells. BMC Complement. Med. Ther. 2020, 20, 68. [Google Scholar] [CrossRef] [PubMed]
- Chu, S.C.; Hsieh, Y.S.; Yu, C.C.; Lai, Y.Y.; Chen, P.N. Thymoquinone induces cell death in human squamous carcinoma cells via caspase activation-dependent apoptosis and LC3-II activation-dependent autophagy. PLoS ONE 2014, 9, e101579. [Google Scholar] [CrossRef] [PubMed]
- Soo, H.C.; Chung, F.F.; Lim, K.H.; Yap, V.A.; Bradshaw, T.D.; Hii, L.W.; Tan, S.H.; See, S.J.; Tan, Y.F.; Leong, C.O.; et al. Cudraflavone C Induces Tumor-Specific Apoptosis in Colorectal Cancer Cells through Inhibition of the Phosphoinositide 3-Kinase (PI3K)-AKT Pathway. PLoS ONE 2017, 12, e0170551. [Google Scholar] [CrossRef] [PubMed]
- Ashburner, M.; Ball, C.A.; Blake, J.A.; Botstein, D.; Butler, H.; Cherry, J.M.; Davis, A.P.; Dolinski, K.; Dwight, S.S.; Eppig, J.T.; et al. Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 2000, 25, 25–29. [Google Scholar] [CrossRef]
- Yi, T.; Cho, S.G.; Yi, Z.; Pang, X.; Rodriguez, M.; Wang, Y.; Sethi, G.; Aggarwal, B.B.; Liu, M. Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways. Mol. Cancer Ther. 2008, 7, 1789–1796. [Google Scholar] [CrossRef]
- Gan, Y.; Zheng, S.; Baak, J.P.; Zhao, S.; Zheng, Y.; Luo, N.; Liao, W.; Fu, C. Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis. Acta Pharm. Sin. B 2015, 5, 590–595. [Google Scholar] [CrossRef]
- Korff, J.M.; Menke, K.; Schwermer, M.; Falke, K.; Schramm, A.; Längler, A.; Zuzak, T.J. Antitumoral Effects of Curcumin (Curcuma longa L.) and Thymoquinone (Nigella sativa L.) on Neuroblastoma Cell Lines. Complement. Med. Res. 2021, 28, 164–168. [Google Scholar] [CrossRef]
- Saddiq, A.A.; El-Far, A.H.; Mohamed Abdullah, S.A.; Godugu, K.; Almaghrabi, O.A.; Mousa, S.A. Curcumin, thymoquinone, and 3, 3′-diindolylmethane combinations attenuate lung and liver cancers progression. Front. Pharmacol. 2022, 13, 936996. [Google Scholar] [CrossRef]
- Zhou, X.; Hao, Q.; Liao, P.; Luo, S.; Zhang, M.; Hu, G.; Liu, H.; Zhang, Y.; Cao, B.; Baddoo, M.; et al. Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator. eLife 2016, 5, e15099. [Google Scholar] [CrossRef]
- Kraus, D.; Glassmann, A.; Golletz, C.; Kristiansen, G.; Winter, J.; Probstmeier, R. Zona Pellucida Protein 2 (ZP2) Is Expressed in Colon Cancer and Promotes Cell Proliferation. Cancers 2021, 13, 1759. [Google Scholar] [CrossRef]
- Gorreja, F.; Rush, S.T.; Kasper, D.L.; Meng, D.; Walker, W.A. The developmentally regulated fetal enterocyte gene, ZP4, mediates anti-inflammation by the symbiotic bacterial surface factor polysaccharide A on Bacteroides fragilis. Am. J. Physiol. Gastrointest. Liver Physiol. 2019, 317, G398–G407. [Google Scholar] [CrossRef] [PubMed]
- Marchetti, D.; Aucoin, R.; Blust, J.; Murry, B.; Greiter-Wilke, A. p75 neurotrophin receptor functions as a survival receptor in brain-metastatic melanoma cells. J. Cell Biochem. 2004, 91, 206–215. [Google Scholar] [CrossRef] [PubMed]
- Zhang, L.; Xiu, X.; Li, Z.; Su, R.; Li, X.; Ma, S.; Ma, F. Coated Porous Microneedles for Effective Intradermal Immunization with Split Influenza Vaccine. ACS Biomater. Sci. Eng. 2023, 9, 6880–6890. [Google Scholar] [CrossRef] [PubMed]
- Wen, J.; Yin, P.; Li, L.; Kang, G.; Ning, G.; Cao, Y.; Gao, F.; Su, Y.; Wu, Y.; Zhang, X. Knockdown of Matrix Metallopeptidase 9 Inhibits Metastasis of Oral Squamous Cell Carcinoma Cells in a Zebrafish Xenograft Model. Biomed. Res. Int. 2020, 2020, 4350783. [Google Scholar] [CrossRef]
- Nirgude, S.; Choudhary, B. Insights into the role of GPX3, a highly efficient plasma antioxidant, in cancer. Biochem. Pharmacol. 2021, 184, 114365. [Google Scholar] [CrossRef]
- Li, X.; Ma, Y.; Wu, J.; Ni, M.; Chen, A.; Zhou, Y.; Dai, W.; Chen, Z.; Jiang, R.; Ling, Y.; et al. Thiol oxidative stress-dependent degradation of transglutaminase2 via protein S-glutathionylation sensitizes 5-fluorouracil therapy in 5-fluorouracil-resistant colorectal cancer cells. Drug Resist. Updat. 2023, 67, 100930. [Google Scholar] [CrossRef]
- Malkomes, P.; Lunger, I.; Oppermann, E.; Abou-El-Ardat, K.; Oellerich, T.; Günther, S.; Canbulat, C.; Bothur, S.; Schnütgen, F.; Yu, W.; et al. Transglutaminase 2 promotes tumorigenicity of colon cancer cells by inactivation of the tumor suppressor p53. Oncogene 2021, 40, 4352–4367. [Google Scholar] [CrossRef]
- Wang, H.; Luo, K.; Tan, L.Z.; Ren, B.G.; Gu, L.Q.; Michalopoulos, G.; Luo, J.H.; Yu, Y.P. p53-induced gene 3 mediates cell death induced by glutathione peroxidase 3. J. Biol. Chem. 2012, 287, 16890–16902. [Google Scholar] [CrossRef]
- Yi, Z.; Jiang, L.; Zhao, L.; Zhou, M.; Ni, Y.; Yang, Y.; Yang, H.; Yang, L.; Zhang, Q.; Kuang, Y.; et al. Glutathione peroxidase 3 (GPX3) suppresses the growth of melanoma cells through reactive oxygen species (ROS)-dependent stabilization of hypoxia-inducible factor 1-α and 2-α. J. Cell Biochem. 2019, 120, 19124–19136. [Google Scholar] [CrossRef]
- Cui, M.; Liu, D.; Xiong, W.; Wang, Y.; Mi, J. ERRFI1 induces apoptosis of hepatocellular carcinoma cells in response to tryptophan deficiency. Cell Death Discov. 2021, 7, 274. [Google Scholar] [CrossRef]
- Yang, X.D.; Cen, Z.D.; Cheng, H.P.; Shi, K.; Bai, J.; Xie, F.; Wu, H.W.; Li, B.B.; Luo, W. L-3-n-Butylphthalide Protects HSPB8 K141N Mutation-Induced Oxidative Stress by Modulating the Mitochondrial Apoptotic and Nrf2 Pathways. Front. Neurosci. 2017, 11, 402. [Google Scholar] [CrossRef] [PubMed]
- Jiang, A.J.; Jiang, G.; Li, L.T.; Zheng, J.N. Curcumin induces apoptosis through mitochondrial pathway and caspases activation in human melanoma cells. Mol. Biol. Rep. 2015, 42, 267–275. [Google Scholar] [CrossRef] [PubMed]
- Zhao, G.; Han, X.; Zheng, S.; Li, Z.; Sha, Y.; Ni, J.; Sun, Z.; Qiao, S.; Song, Z. Curcumin induces autophagy, inhibits proliferation and invasion by downregulating AKT/mTOR signaling pathway in human melanoma cells. Oncol. Rep. 2016, 35, 1065–1074. [Google Scholar] [CrossRef] [PubMed]
- Han, J.; Pan, X.Y.; Xu, Y.; Xiao, Y.; An, Y.; Tie, L.; Pan, Y.; Li, X.J. Curcumin induces autophagy to protect vascular endothelial cell survival from oxidative stress damage. Autophagy 2012, 8, 812–825. [Google Scholar] [CrossRef]
- Li, Y.Q.; Sun, F.Z.; Li, C.X.; Mo, H.N.; Zhou, Y.T.; Lv, D.; Zhai, J.T.; Qian, H.L.; Ma, F. RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer. Mil. Med. Res. 2023, 10, 34. [Google Scholar] [CrossRef]
- Luo, J.; Kibriya, M.G.; Chen, H.; Kim, K.; Ahsan, H.; Olopade, O.I.; Olopade, C.S.; Aschebrook-Kilfoy, B.; Huo, D. A metabolome-wide case-control study of african american breast cancer patients. BMC Cancer 2023, 23, 183. [Google Scholar] [CrossRef]
- Yang, J.; Shi, C.; Cheng, Y.; Zhu, Y.; Yang, X.; Liang, Y.; Liang, H.; Lin, Q.; Li, M.; Xun, J.; et al. Effective in vivo reactivation of HIV-1 latency reservoir via oral administration of EK-16A-SNEDDS. Eur. J. Pharm. Biopharm. 2024, 201, 114353. [Google Scholar] [CrossRef]
- Qi, Y.S.; Xiao, M.Y.; Xie, P.; Xie, J.B.; Guo, M.; Li, F.F.; Piao, X.L. Comprehensive serum metabolomics and network analysis to reveal the mechanism of gypenosides in treating lung cancer and enhancing the pharmacological effects of cisplatin. Front. Pharmacol. 2022, 13, 1070948. [Google Scholar] [CrossRef]
Comparison | Upregulated Genes | Downregulated Genes |
---|---|---|
TQ vs. Control | 0 | 2 |
TQ vs. CU | 50 | 15 |
TQ vs. (TQ + CU) | 284 | 114 |
CU vs. Control | 37 | 31 |
CU vs. (TQ + CU) | 211 | 74 |
(TQ + CU) vs. Control | 269 | 283 |
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Mohd, H.; Michniak-Kohn, B. Synergistic Anti-Cancer Effects of Curcumin and Thymoquinone Against Melanoma. Antioxidants 2024, 13, 1573. https://doi.org/10.3390/antiox13121573
Mohd H, Michniak-Kohn B. Synergistic Anti-Cancer Effects of Curcumin and Thymoquinone Against Melanoma. Antioxidants. 2024; 13(12):1573. https://doi.org/10.3390/antiox13121573
Chicago/Turabian StyleMohd, Hana, and Bozena Michniak-Kohn. 2024. "Synergistic Anti-Cancer Effects of Curcumin and Thymoquinone Against Melanoma" Antioxidants 13, no. 12: 1573. https://doi.org/10.3390/antiox13121573
APA StyleMohd, H., & Michniak-Kohn, B. (2024). Synergistic Anti-Cancer Effects of Curcumin and Thymoquinone Against Melanoma. Antioxidants, 13(12), 1573. https://doi.org/10.3390/antiox13121573