Quercetin synergistically potentiates the anti-metastatic effect of 5-fluorouracil on the MDA-MB-231 breast cancer cell line | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 9، دوره 24، شماره 7، مهر 2021، صفحه 928-934 اصل مقاله (939.81 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2021.56559.12629 | ||
| نویسندگان | ||
| Mohammadreza Roshanazadeh1؛ hossein babaahmadi rezaei2؛ Mojtaba Rashidi* 1 | ||
| 1Cellular and molecular Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran | ||
| 2Hyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran | ||
| چکیده | ||
| Objective(s): Breast cancer (BC) cells’ ability to metastasize to other tissues increases mortality. The Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) facilitate cancer cell migration. 5-fluorouracil is a frequently applied chemotherapeutic agent in cancer treatment with destructive side effects on normal tissues. Hence, researchers have focused on finding a way to reduce the dose of chemotherapeutic drugs. Quercetin, a natural polyphenolic compound, has inhibitory effects on proliferation and migration of tumor cells. This study evaluated the effect of the combination of Quercetin and 5-fluorouracil on migration of the MDA-MB-231 breast cancer cell line. Materials and Methods: The effect of Quercetin, 5-fluorouracil , and their combination on MDA-MB-231 breast cancer cell proliferation was investigated through MTT assay. Inhibition of tumor cell migration was examined by wound healing assay. Finally, the effect of treatments on gene expression of MMP-2 and MMP-9 was evaluated by quantitative real-time PCR. Results: The IC50 values for Quercetin and 5-fluorouracil after 48 hr treatment were 295 μM and 525 μM, respectively. The combination index (CI) for Quercetin and 5-fluorouracil was <1, indicating synergy between them. The combination of Quercetin plus 5-fluorouracil resulted in a significant reduction in migration rate and MMP-2 and MMP-9 gene expressions of MDA-MB-231 cancer cells compared with the individual application of 5-FU. Conclusion: Quercetin enhances the suppressory effect of 5-fluorouracil on migration of BC cells. The combination of Quercetin and 5-fluorouracil can be an attractive field for future studies. | ||
| کلیدواژهها | ||
| 5-fluorouracil؛ Anti-metastatic effect؛ Breast cancer؛ Quercetin؛ Synergism | ||
| مراجع | ||
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1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. 2. Ismail-Khan R, Bui MM. A review of triple-negative breast cancer. Cancer Control 2010;17:173-176. 3. Nedeljković M, Damjanović A. Mechanisms of chemotherapy resistance in triple-negative breast cancer-how we can rise to the challenge. Cells 2019;8:957. 4. Geiger TR, Peeper DS. Metastasis mechanisms. Biochim Biophys Acta 2009;1796:293-308. 5. Gupta GP, Massagué J. Cancer metastasis: building a framework. Cell 2006;127:679-695. 6. Lord SJ, Kiely BE, Pearson S-A, Daniels B, O’Connell DL, Beith J, et al. Metastatic breast cancer incidence, site and survival in Australia, 2001–2016: a population-based health record linkage study protocol. BMJ Open 2019;9:e026414 7. Woodhouse EC, Chuaqui RF, Liotta LA. General mechanisms of metastasis. Cancer 1997;80:1529-1537. 8. Ahmad A, Hart I. Mechanisms of metastasis. Crit Rev Oncol Hematol 1997;26:163-173. 9. Donnelly SK, Cabrera R, Mao SP, Christin JR, Wu B, Guo W, et al. Rac3 regulates breast cancer invasion and metastasis by controlling adhesion and matrix degradation. J Cell Biol 2017;216:4331-4349. 10. Erler JT, Weaver VM. Three-dimensional context regulation of metastasis. Clin Exp Metastasis 2009;26:35-49. 11. Kleiner DE, Stetler-Stevenson WG. Matrix metalloproteinases and metastasis. Cancer Chemother Pharmacol 1999;43:S42-S51. 12. Köhrmann A, Kammerer U, Kapp M, Dietl J, Anacker J. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature. BMC Cancer 2009;9:1-20. 13. Eiseler T, Döppler H, Yan IK, Goodison S, Storz P. Protein kinase D1 regulates matrix metalloproteinase expression and inhibits breast cancer cell invasion. Breast Cancer Res 2009;11:1-12. 14. Shewach DS, Kuchta RD. Introduction to cancer chemotherapeutics. Chem Rev 2009;109:2859-2861. 15. Altun I, Sonkaya A. The most common side effects experienced by patients were receiving first cycle of chemotherapy. Iran J Public Health 2018;47:1218-1219. 16. Love RR, Leventhal H, Easterling DV, Nerenz DR. Side effects and emotional distress during cancer chemotherapy. Cancer 1989;63:604-612. 17. Monsuez J-J, Charniot J-C, Vignat N, Artigou J-Y. Cardiac side-effects of cancer chemotherapy. Int J Cardiol 2010;144:3-15. 18. Wu T, Munro AJ, Guanjian L, Liu GJ. Chinese medical herbs for chemotherapy side effects in colorectal cancer patients. Cochrane Database Syst Rev 2005:1-24 19. Boik J. Natural Compounds in Cancer Therapy: Oregon Medical Press Princeton, MN 2001. 20. Lin S-R, Fu Y-S, Tsai M-J, Cheng H, Weng C-F. Natural compounds from herbs that can potentially execute as autophagy inducers for cancer therapy. Int J Mol Sci 2017;18:1412. 21. Lin SR, Chang CH, Hsu CF, Tsai MJ, Cheng H, Leong MK, et al. Natural compounds as potential adjuvants to cancer therapy: Preclinical evidence. Br J Pharmacol 2020;177:1409-1423. 22. Nobili S, Lippi D, Witort E, Donnini M, Bausi L, Mini E, et al. Natural compounds for cancer treatment and prevention. Pharmacol Res 2009;59:365-378. 23. von Schwarzenberg K, Vollmar AM. Targeting apoptosis pathways by natural compounds in cancer: Marine compounds as lead structures and chemical tools for cancer therapy. Cancer Lett 2013;332:295-303. 24. Amin AR, Wang D, Zhang H, Peng S, Shin HJC, Brandes JC, et al. Enhanced anti-tumor activity by the combination of the natural compounds (−)-epigallocatechin-3-gallate and luteolin: potential role of p53. J Biol Chem 2010;285:34557-34565. 25. Lichota A, Gwozdzinski K. Anticancer activity of natural compounds from plant and marine environment. Int J Mol Sci 2018;19:3533. 26. Rejhová A, Opattová A, Čumová A, Slíva D, Vodička P. Natural compounds and combination therapy in colorectal cancer treatment. Eur J Med Chem 2018;144:582-594. 27. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003;3:330-338. 28. Latif YA, El-Bana M, Hussein J, El-Khayat Z, Farrag AR. Effects of resveratrol in combination with 5-fluorouracil on N-methylnitrosourea-induced colon cancer in rats. Comp Clin Path 2019;28:1351-1362. 29. Lee SH, Koo BS, Park SY, Kim YM. Anti‑angiogenic effects of resveratrol in combination with 5‑fluorouracil on B16 murine melanoma cells. Mol Med Rep 2015;12:2777-2783. 30. López EP-F, García FG, Jornet PL. Combination of 5-Florouracil and polyphenol EGCG exerts suppressive effects on oral cancer cells exposed to radiation. Arch Oral Biol 2019;101:8-12. 31. Mohan A, Narayanan S, Sethuraman S, Krishnan UM. Novel resveratrol and 5-fluorouracil coencapsulated in PEGylated nanoliposomes improve chemotherapeutic efficacy of combination against head and neck squamous cell carcinoma. Biomed Res Int 2014;2014:1-14 32. Tang H, Zeng L, Wang J, Zhang X, Ruan Q, Wang J, et al. Reversal of 5-fluorouracil resistance by EGCG is mediate by inactivation of TFAP2A/VEGF signaling pathway and down-regulation of MDR-1 and P-gp expression in gastric cancer. Oncotarget 2017;8:82842. 33. Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA. Protective effect of quercetin in primary neurons against Aβ (1-42): relevance to Alzheimer’s disease. J Nutr Biochem 2009;20:269-275. 34. Larson AJ, Symons JD, Jalili T. Therapeutic potential of quercetin to decrease blood pressure: review of efficacy and mechanisms. Adv Nutr 2012;3:39-46. 35. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2009;2:270-278. 36. Angst E, Park JL, Moro A, Lu Q-Y, Lu X, Li G, et al. The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo. Pancreas 2013;42:223. 37. Dihal AA, de Boer VC, van der Woude H, Tilburgs C, Bruijntjes JP, Alink GM, et al. Quercetin, but not its glycosidated conjugate rutin, inhibits azoxymethane-induced colorectal carcinogenesis in F344 rats. J Nutr 2006;136:2862-2867. 38. Maciejczyk A, Surowiak P. Quercetin inhibits proliferation and increases sensitivity of ovarian cancer cells to cisplatin and paclitaxel. Ginekol Pol 2013;84:590-595 39. Sengupta A, Ghosh S, Das S. Modulation of DMBA induced genotoxicity in bone marrow by quercetin during skin carcinogenesis. J Exp Clin Cancer Res: CR 2001;20:131-134. 40. Senthilkumar K, Arunkumar R, Elumalai P, Sharmila G, Gunadharini DN, Banudevi S, et al. Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC‐3). Cell Biochem Funct 2011;29:87-95. 41. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-249 42. Hua H, Li M, Luo T, Yin Y, Jiang Y. Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci 2011;68:3853-3868. 43. Kuczynski EA, Sargent DJ, Grothey A, Kerbel RS. Drug rechallenge and treatment beyond progression-implications for drug resistance. Nat Rev Clin Oncol 2013;10:571. 44. Chuang‑Xin L, Wen‑Yu W, Yao C, Xiao‑Yan L, Yun Z. Quercetin enhances the effects of 5‑fluorouracil‑mediated growth inhibition and apoptosis of esophageal cancer cells by inhibiting NF‑κB. Oncol Lett 2012;4:775-778. 45. M Elsadek BE, Abdel Aziz MA, M El-Deek SE, M Mahdy MM, Hussein MR. Combination therapy with quercetin and 5-Fluorouracil ameliorates 1, 2-Dimethylhydrazine induced carcinogenesis in the colon of wistar rats. Bulletin of Egyptian Soc Physiol Sci 2017;37:227-244. 46. Sundaram MK, Raina R, Afroze N, Dhupkar A, Kaur NP, Arte A, et al. Combinational use of phytochemicals and chemotherapeutic drugs enhance their therapeutic potential on human cervical cancer cells. Int J Cancer Manag 2019;12:e91783. 47. Xavier CP, Lima CF, Rohde M, Pereira-Wilson C. Quercetin enhances 5-fluorouracil-induced apoptosis in MSI colorectal cancer cells through p53 modulation. Cancer Chemother Pharmacol 2011;68:1449-1457. 48. Chung SS, Dutta P, Austin D, Wang P, Awad A, Vadgama JV. Combination of resveratrol and 5-flurouracil enhanced anti-telomerase activity and apoptosis by inhibiting STAT3 and Akt signaling pathways in human colorectal cancer cells. Oncotarget 2018;9:32943. 49. Riahi-Chebbi I, Souid S, Othman H, Haoues M, Karoui H, Morel A, et al. The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells. Sci Rep 2019;9:1-20. 50. Mook OR, Frederiks WM, Van Noorden CJ. The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys Acta (BBA)-Reviews on Cancer 2004;1705:69-89. 51. Merdad A, Karim S, Schulten H-J, Dallol A, Buhmeida A, Al-Thubaity F, et al. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis. Anticancer Res 2014;34:1355-1366. 52. El-Badrawy MK, Yousef AM, Shaalan D, Elsamanoudy AZ. Matrix metalloproteinase-9 expression in lung cancer patients and its relation to serum mmp-9 activity, pathologic type, and prognosis. J Bronchology Interv Pulmonol 2014;21:327-334. 53. Hung W-C, Tseng W-L, Shiea J, Chang H-C. Skp2 overexpression increases the expression of MMP-2 and MMP-9 and invasion of lung cancer cells. Cancer lett 2010;288:156-161. 54. Huang L, Cai YJ, Lung I, Leung BC, Burd A. A study of the combination of triamcinolone and 5-fluorouracil in modulating keloid fibroblasts in vitro. J Plast Reconstr Aesthet Surg 2013;66:e251-e259. 55. Yang Y, Ma L, Xu Y, Liu Y, Li W, Cai J, et al. Enalapril overcomes chemoresistance and potentiates antitumor efficacy of 5-FU in colorectal cancer by suppressing proliferation, angiogenesis, and NF-κB/STAT3-regulated proteins. Cell Death Dis 2020;11:1-13. 56. Fu Z, Ma K, Dong B, Zhao C, Che C, Dong C, et al. The synergistic antitumor effect of Huaier combined with 5-Florouracil in human cholangiocarcinoma cells. BMC Complement Altern Med 2019;19:1-12. 57. Zhang L, Chen H, Wang M, Song X, Ding F, Zhu J, et al. Effects of glabridin combined with 5-fluorouracil on the proliferation and apoptosis of gastric cancer cells. Oncol Lett 2018;15:7037-7045. 58. Afrin S, Giampieri F, Forbes-Hernández TY, Gasparrini M, Amici A, Cianciosi D, et al. Manuka honey synergistically enhances the chemopreventive effect of 5-fluorouracil on human colon cancer cells by inducing oxidative stress and apoptosis, altering metabolic phenotypes and suppressing metastasis ability. Free Radic Biol Med 2018;126:41-54. | ||
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