Abstract

Higher plants are prominent sources for several bioactive chemical constituents (secondary metabolites) who include photochemical, flavoring agents, fragrant molecules, and food additives. According to WHO estimates, it has been reported that more than 80% of population in developing countries prefer these natural bioactive active compounds for their primary health requirement. At present, conventional chemotherapy is constrained due to the nonselective toxicity to human organs and their usage is limited now a days. In a recent survey, more than 60% of cancer patients have been preferring adjuvant phototherapy along with chemotherapy. Thus, photochemical are being widely used as anticancer agents to target specific pathological pathways underlying cancer with low toxic profiles and side effects. These photochemical are cost-effective and easily accessible to the public to treat cancer diseases. These bioactive photochemical are meticulously belongs to secondary metabolites such as alkaloids, flavonoids, polyphenols.Among them, the flavonoids are polyphenolic substances, which are found in all parts of the plant such as flowers, fruits, leaves, roots, seeds, and bark. They possess high medicinal properties like being anti-cancer, anti-hypertensive, anti-inflammatory, anti-obesity, anti-malarial, antioxidant agents. Quercetin is major flavones associated with a profound antioxidant and medicinal property to prevent the oxidation of lipids in vitro and in vivo, and also exhibits direct proapoptotic effects on tumor cells. This compound has proven efficacy in targeting several cancer cells of breast, colon, prostate, ovarian, and lung tumor in vitro. The present review focuses on the effect of quercetin in cancer therapy.

Keywords

Quercetin, cancer, antioxidant, anticancer activity,

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References

  1. He L, Gu J, Lim LY, Yuan ZX, Mo J. Nanomedicine-mediated therapies to target breast cancer stem cells. Front Pharmacol 2016; 7: 313.
  2. Qin W, Huang G, Chen Z, Zhang Y. Nanomaterials in targeting cancer stem cells for cancer therapy. Front Pharmacol 2017; 8: 1.
  3. Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RG, Barzi A, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin 2017; 67(3): 177-93.
  4. Krishnamurthi K. 17-screening of natural products for anticancer and antidiabetic properties. Cancer 2007; 3: 4.
  5. F. S. Liu, “Mechanisms of chemotherapeutic drug resistance in cancer therapy—a quick review,” Taiwanese Journal of Obstetrics and Gynecology, vol. 48, no. 3, pp. 239–244, 2009.
  6. H.Osiecki, Cancer: ANutritional, Biochemical Approach, Bioconcepts Publishing, 2002.
  7. R. M. Howes, “Dangers of antioxidants in cancer patients: a review,” Philica, Article ID 153, 2009.
  8. J. Sagar, B. Chaib, K. Sales, M. Winslet, and A. Seifalian, “Role of stem cells in cancer therapy and cancer stem cells: a review,” Cancer Cell International, vol. 7, pp. 9–19, 2007.
  9. G. L. Nicolson, “Lipid replacement/antioxidant therapy as an adjunct supplement to reduce the adverse effects of cancer therapy and restore mitochondrial function,” Pathology and Oncology Research, vol. 11, no. 3, pp. 139–144, 2005.
  10. R. W. Johnstone, A. A. Ruefli, and S. W. Lowe, “Apoptosis: a link between cancer genetics and chemotherapy,” Cell, vol. 108, no. 2, pp. 153–164, 2002.
  11. C. L. Loprinzi, D. L. Barton, A. Jatoi et al., “Symptom controlNtrials: a 20-year experience,” Journal of Supportive Oncology, vol. 5, no. 3, pp. 119–128, 2007.
  12. B. U. Philips, The Case for Cancer Nutritional Support, The Cancer Nutrition Network of Texas, 1999.
  13. Griesbach R (2005) Biochemistry and genetics of flower color. Plant Breed Rev 25, 89–114.
  14. Harborne, J. B. In Plant Flavonoids in Biology and Medicine; Cody, V., Middleton, E., Harborne, J. B., Eds.; Alan R. Liss: New York, 1986; pp 15-24.
  15. Cody V. Plant Flavonoids in Biology and Medicine. ProgClinBiol Res 1986;213.
  16. Baghel, S. S., Shrivastava, N., Baghel, R. S., Agrawal, P., & Rajput, S. (2012). A review of quercetin: antioxidant and anticancer properties. World J Pharm Pharmaceutical Sci, 1(1), 146-60.
  17. Braganhol, E.,Zamin,L.L.,Canedo,A.D.,Horn,F.,Tamajusuku,A.S.,Wink,M.R., Salbego, C.,Battastini,A.M.,2006.Antiproliferative effect of quercetin in the human U138MG glioma cell line.AnticancerDrugs17,663–671.
  18. Xie, X.,Yin,J.,Jia,Q.,Wang,J.,Zou,C.,Brewer,K.J.,Colombo,C.,Wang,Y.,Huang,G., Shen, J.,2010.Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma celllineU2-OS/MTX300via mitochondrial dysfunction and dephosphorylation of Akt.OncologyReports26,687–693.
  19. VidyPriyadarsini,R.,SenthilMurugan,R.,Maitreyi,S.,Ramalingam,K.,Karunagaran, D.,Nagini,S.,2010. The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-kB inhibition. European Journal of Pharmacology 649, 84–89.
  20. Hsieh, T.C., Wu, J.M., 2009. Targeting CWR22Rv1 prostate cancer cellproliferation and gene expression by combinations of the phytochemicals EGCG, genistein and quercetin.AnticancerResearch29, 4025–4032.
  21. Choi, E.,Bae,S.M.,Ahn,W.S.,2008.Antiproliferative effects of quercetin through cell cycle arrest and apoptosis in human breast cancer MDA-MB-453cells. Archives of Pharmacal Research31,1281–1285.
  22. Duraj, J.,Zazrivcova,K.,Bodo,J.,Sulikova,M.,Sedlak,J.,2005.Flavonoid quercetin, but not apigenin or luteolin, induced apoptosis in human myeloid leukemia cells andtheirresistantvariants.Neoplasma52,273–279.
  23. Lamson, D.W.,Brignall, M.S.,2000.Antioxidants and cancer III: quercetin. Alter- native MedicineReview5, 196–208.
  24. Gibellini, L.,Pinti,M.,Nasi,M.,Montagna,J.P.,DeBiasi,S.,Roat,E.,Bertoncelli,L., Cooper, E.L.,Cossarizza,A.,2011. Quercetin and Cancer Chemoprevention. Evidence-based Complementary and Alternative Medicine 2011: ArticleID 591356, http://dx.doi.org/10.1093/ecam/neq053.
  25. Minaei, A., Sabzichi, M., Ramezani, F., Hamishehkar, H., &Samadi, N. (2016). Co?delivery with nano?quercetin enhances doxorubicin?mediated cytotoxicity against MCF?7 cells. Molecular Biology Reports, 43, 99–105.
  26. Suksiriworapong, J., Phoca, K., Ngamsom, S., Sripha, K., Moongkarndi, P., &Junyaprasert, V. B. (2016). Comparison of poly (??caprolactone) chain lengths of poly (??caprolactone)?co?d???tocopheryl?poly (ethylene glycol) 1000 succinate nanoparticles for enhancement of quercetin delivery to SKBR3 breast cancer cells. European Journal of Pharmaceutics and Biopharmaceutics, 101, 15–24.
  27. Chen, F. Y., Cao, L. F., Wan, H. X., Zhang, M. Y., Cai, J. Y., Shen, L. J., … Zhong, H. (2015). Quercetin enhances adriamycin cytotoxicity through induction of apoptosis and regulation of mitogen?activated protein kinase/extracellular signal?regulated kinase/c?Jun N?terminal kinase signaling in multidrug?resistant leukemia K562 cells. Molecular Medicine Reports, 11, 341–348.
  28. Balakrishnan, S., Bhat, F. A., Raja Singh, P., Mukherjee, S., Elumalai, P., Das, S., … Arunakaran, J. (2016). Gold nanoparticle?conjugated quercetin inhibits epithelial?mesenchymal transition, angiogenesis, and invasiveness via EGFR/VEGFR?2?mediated pathway in breast cancer. Cell Proliferation, 49, 678–697.
  29. Han, M., Song, Y., & Zhang, X. (2016). Quercetin suppresses the migration and invasion in human colon cancer caco?2 cells through regulating toll?like receptor 4/nuclear factor?kappa B pathway. Pharmacognosy Magazine, 12, S237–S244.
  30. Seo, H. S., Ku, J. M., Choi, H. S., Choi, Y. K., Woo, J. K., Kim, M., … Ko, S. G. (2016). Quercetin induces caspase?dependent extrinsic apoptosis through inhibition of signal transducer and activator of transcription 3 signaling in HER2?overexpressing BT?474 breast cancer cells. Oncology Reports, 36, 31–42.
  31. Khan, F., Niaz, K., Maqbool, F., Ismail Hassan, F., Abdollahi, M., NagulapalliVenkata, K., ... &Bishayee, A. (2016). Molecular targets underlying the anticancer effects of quercetin: an update. Nutrients, 8(9), 529.
  32. Murakami, A., Ashida, H., &Terao, J. (2008). Multitargeted cancer prevention by quercetin. Cancer Letters, 269, 315–325.
  33. Caltagirone, S.,Rossi,C.,Poggi,A.,Ranelletti,F.O.,Natali,P.G.,Brunetti,M.,Aiello, F.B., Piantelli,M.,2000. Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. International Journal of Cancer87,595–600.
  34. Yang, C.S.; Landau, J.M.; Huang, M.T.; Newmark, H.L. Inhibition of carcinogenesis by dietary polyphenolic compounds. Annu. Rev. Nutr. 2001, 21, 381–406.
  35. Quagliariello, V., Armenia, E., Aurilio, C., Rosso, F., Clemente, O., de Sena, G., … Barbarisi, A. (2016). New treatment of medullary and papillary human thyroid cancer: Biological effects of hyaluronic acid hydrogel loaded with quercetin alone or in combination to an inhibitor of aurora kinase. The Journal of Cellular Physiology, 231, 1784–1795.
  36. Kee, J. Y., Han, Y. H., Kim, D. S., Mun, J. G., Park, J., Jeong, M. Y., … Hong, S. H. (2016). Inhibitory effect of quercetin on colorectal lung metastasis through inducing apoptosis, and suppression of metastatic ability. Phytomedicine, 23(13), 1680–1690.
  37. Oršoli?, N., & Car, N. (2014). Quercetin and hyperthermia modulate cisplatin? induced DNA damage in tumor and normal tissues in vivo. Tumour Biology, 35, 6445–6454.
  38. Dihal, A.A.; van der Woude, H.; Hendriksen, P.J.; Charif, H.; Dekker, L.J.; IJsselstijn, L.; De Boer, V.C.J.; Alink, G.M.; Burgers, P.C.; Rietjens, I.M.C.M. Transcriptome and proteome profiling of colon mucosa from quercetin fed F344 rats point to tumor preventive mechanisms, increased mitochondrial fatty acid degradation and decreased glycolysis. Proteomics 2008, 8, 45–61.
  39. Nigro JM, Baker SJ, Preisinger AC, et al. Mutations in the p53 gene occur in diverse human tumour types. Nature, 1989;342:705-8.
  40. Rauf, A., Imran, M., Khan, I. A., ur?Rehman, M., Gilani, S. A., Mehmood, Z., & Mubarak, M. S. (2018). Anticancer potential of quercetin: A comprehensive review. Phytotherapy research, 32(11), 2109-2130.
  41. Avila MA, Velasco JA, Cansado J, Notario V. Quercetin mediates the downregulation of mutant p53 in the human breast cancer cell line MDA-MB468. Cancer Res, 1994;54:2424-8.
  42. Avila MA, Velasco JA, Harter KW, et al. Quercetin as a modulator of the cellular neoplastic phenotype. AdvExpl Med Biol, 1996;401:101-10.
  43. Liao, H., Bao, X., Zhu, J., Qu, J., Sun, Y., Ma, X., … Zhen, Y. (2015). O Alkylated derivatives of quercetin induce apoptosis of MCF?7 cells via a caspase?independent mitochondrial pathway. Chemico?Biological Interactions, 242, 91–98.
  44. Ranganathan, S., Halagowder, D., &Sivasithambaram, N. D. (2015). Quercetin suppresses twist to induce apoptosis in MCF?7 breast cancer cells. PLoS One, 10, e0141370.
  45. Yoshida M, Yamamoto M, Nikaido T. Quercetin arrests human leukemic T-cells in late G1phase of the cell cycle. Cancer Res, 1992; 52: 6676-81.
  46. Yoshida M, Sakai T, Hosokawa N, et al. The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Lett, 1990; 260:10-13.
  47. Zhao, J., Liu, J., Wei, T., Ma, X., Cheng, Q., Huo, S., … Liang, X. J. (2017). Quercetin?loaded nanomicelles to circumvent human castration?resistant prostate cancer in vitro and in vivo. Nanoscale, 8, 5126–5138.