ANTI-CANCER ACTIVITY OF QUERCETIN VIA APOPTOSIS INDUCTION PATHWAYS IN HUMAN BREAST CANCER CELL LINES-A SYSTEMATIC REVIEW AND META-ANALYSIS


ANTI-CANCER ACTIVITY OF QUERCETIN VIA APOPTOSIS INDUCTION PATHWAYS IN HUMAN BREAST CANCER CELL LINES-A SYSTEMATIC REVIEW AND META-ANALYSIS


Rawdha Benziane; Bunmi Ibrahim*

School of Allied Health Sciences. De Montfort University, Leicester. United Kingdom


A systematic review and meta-analysis were conducted to summarize and review the current literature surrounding quercetin in breast cancer and evaluate its efficacy as an anticancer agent in human breast cancer cell lines. Electronic databases, PUBMED, WEB OF SCIENCE and MEDLINE were systematically searched in December 2020 using the key terms, Quercetin AND Breast cancer AND apoptosis OR cell cycle. Fourteen papers surrounding effects of quercetin on cell viability were obtained. Risk of bias assessment revealed that most papers were reliable. Three meta-analyses were conducted to confirm the efficacy of quercetin at the concentrations of 40-50 µM, 100µM, and >100µM (120- 200 µM). Two subgroup analyses on incubation time and cell type were performed to ascertain whether these factors affect mechanisms of quercetin. Results showed that the decrease in percentage cell viability is directly proportional to increasing concentration. The greatest decrease in cell viability was observed in 100 µM (Risk Ratio (RR) = 0.56; p<0.00001), followed by 100 µM (RR= 0.74) and then 40-50 µM (RR=0.79). However, effects of quercetin may be determined by other factors such as incubation time or a particular cell type signaling cascade. Subgroup analysis revealed that significant differences between 24 and 48 hours were not observed. MCF7 cells showed to be most sensitive to actions of quercetin (p< 0.0001). It was concluded that there is enough information surrounding the cytotoxic effects of quercetin to be progressed forward, however optimal doses that are physiologically relevant and safe in humans should be elucidated.


Keywords: quercetin, breast cancer cells, apoptosis, meta-analysis, systematic review, cell viability

Free Full-text PDF


How to cite this article:

Rawdha Benziane, Bunmi Ibrahim. Anti-cancer activity of quercetin via apoptosis induction pathways in human breast cancer cell lines-a systematic review and meta-analysis. Journal of Pharmaceutical Research and Reviews, 2022; 6:23. DOI: 10.28933/jprr-2021-09-2805


References:

1.Abdal Dayem, A., Choi, H.Y., Yang, G., Kim, K., Saha, S.K. and Cho, S. (2016) ‘The anti-cancer effect of polyphenols against breast cancer and cancer stem cells: molecular mechanisms’, Nutrients, 8(9), pp. 581. 1
2.Ahmad, A. (2019) Breast Cancer Metastasis and Drug Resistance: Challenges and Progress. Springer. 2
3.Ahn, J., Lee, H., Kim, S., Park, J. and Ha, T. (2008) ‘The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways’, Biochemical and biophysical research communications, 373(4), pp. 545-549. 3
4.Ahrar, S., Hwang, M., Duncan, P.N. and Hui, E.E. (2014) ‘Microfluidic serial dilution ladder’, Analyst, 139(1), pp. 187- 190. 4
5.Andrade, C. (2015) ‘Understanding relative risk, odds ratio, and related terms: as simple as it can get’, The Journal of clinical psychiatry, 76(7), pp. 857-861. 5
6.Batra, P. and Sharma, A.K. (2013) ‘Anti-cancer potential of flavonoids: recent trends and future perspectives’, 3 Biotech, 3(6), pp. 439-459. 6
7.Brisdelli, F., Bennato, F., Bozzi, A., Cinque, B., Mancini, F. and Iorio, R. (2014) ‘ELF-MF attenuates quercetin-induced apoptosis in K562 cells through modulating the expression of Bcl-2 family proteins’, Molecular and cellular biochemistry, 397(1), pp. 33-43. 7
8.Brunetti, A. and Manfioletti, G. (2019) ‘Hormone Receptors and Breast Cancer’, Frontiers in endocrinology, 10, pp. 205. 8
9.Budihardjo, I., Oliver, H., Lutter, M., Luo, X. and Wang, X. (1999) ‘Biochemical pathways of caspase activation during apoptosis’, Annual Review of Cell and Developmental Biology, 15(1), pp. 269-290. 9
10.Cai, X., Fang, Z., Dou, J., Yu, A. and Zhai, G. (2013a) ‘Bioavailability of quercetin: problems and promises’, Current medicinal chemistry, 20(20), pp. 2572- 2582. 10
11.Chaicharoenaudomrung, N., Kunhorm, P. and Noisa, P. (2019) ‘Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling’, World journal of stem cells, 11(12), pp. 1065. 12
12.Chien, S., Wu, Y., Chung, J., Yang, J., Lu, H., Tsou, M., Wood, W.G., Kuo, S. and Chen, D. (2009) ‘Quercetin-induced apoptosis acts through mitochondrial-and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells’, Human & experimental toxicology, 28(8), pp. 493-50393
13.Chou, C., Yang, J., Lu, H., Ip, S., Lo, C., Wu, C., Lin, J., Tang, N., Chung, J. and Chou, M. (2010) ‘Quercetin- mediated cell cycle arrest and apoptosis involving activation of a caspase cascade through the mitochondrial pathway in human breast cancer MCF-7 cells’, Archives of Pharmacal Research, 33(8), pp. 1181-1191. 13
14.Dai, X., Cheng, H., Bai, Z. and Li, J. (2017) ‘Breast cancer cell line classification and its relevance with breast tumor subtyping’, Journal of Cancer, 8(16), pp. 3131. 14
15.Dechsupa, S., Kothan, S., Vergote, J., Leger, G., Martineau, A., Beranger, S., Kosanlavit, R., Moretti, J. and Mankhetkorn, S. (2007) ‘Quercetin, Siamois 1 and Siamois 2 induce apoptosis in human breast cancer MDA-mB-435 cells xenograft in vivo’, Cancer biology & therapy, 6(1), pp. 56- 61. 15
16.Deng, X., Song, H., Zhou, Y., Yuan, G. and Zheng, F. (2013) ‘Effects of quercetin on the proliferation of breast cancer cells and expression of survivin in vitro’, Experimental and therapeutic medicine, 6(5), pp. 1155-1158. 16
17.Denyer, D. and Tranfield, D. (2009) ‘Producing a systematic review.’, . 17
18.Desai, A.G., Qazi, G.N., Ganju, R.K., E El-Tamer, M., Singh, J., Saxena, A.K., Bedi, Y.S., Taneja, S.C. and Bhat, H.K. (2008a) ‘Medicinal plants and cancer chemoprevention’, Current Drug Metabolism, 9(7), pp. 581- 591. 18
20.Devipriya, S., Vani, G., Ramamurthy, N. and Shyamaladevi,C.S. (2006) ‘Regulation of intracellular calcium levels and urokinase activity in MDA MB 231 cells by quercetin’, Chemotherapy, 52(2), pp. 60-65. 20
21.Dhumale, S.S., Waghela, B.N. and Pathak, C. (2015) ‘Quercetin protects necrotic insult and promotes apoptosis by attenuating the expression of RAGE and its ligand HMGB1 in human breast adenocarcinoma cells’, IUBMB life, 67(5), pp. 361-373. 21
22.Duo, J., Ying, G., Wang, G. and Zhang, L. (2012) ‘Quercetin inhibits human breast cancer cell proliferation and induces apoptosis via Bcl-2 and Bax regulation’, Molecular medicine reports, 5(6), pp. 1453-1456. 22
23.Elmore, S. (2007) ‘Apoptosis: a review of programmed cell death’, Toxicologic pathology, 35(4), pp. 495-516. 23
24.Eriksen, M.B. and Frandsen, T.F. (2018) ‘The impact of patient, intervention, comparison, outcome (PICO) as a search strategy tool on literature search quality: a systematic review’, Journal of the Medical Library Association: JMLA, 106(4), pp. 420. 24
25.Ezzati, M., Yousefi, B., Velaei, K. and Safa, A. (2020) ‘A review on anti-cancer properties of Quercetin in breast cancer’, Life Sciences, 248, pp. 117463. 25
26.Ferry, D.R., Smith, A., Malkhandi, J., Fyfe, D.W., deTakats, P.G., Anderson, D., Baker, J. and Kerr, D.J. (1996) ‘Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition.’, Clinical cancer research, 2(4), pp. 659-668. 26
27.Fu, Z. and Tindall, D.J. (2008) ‘FOXOs, cancer and regulation of apoptosis’, Oncogene, 27(16), pp. 2312-2319. 27
28.Gomes, I.B., Porto, M.L., Santos, M.C.L., Campagnaro, B.P., Pereira, T.M., Meyrelles, S.S. and Vasquez, E.C. (2014) ‘Renoprotective, anti-oxidative and anti-apoptotic effects of oral low-dose quercetin in the C57BL/6J model of diabetic nephropathy’, Lipids in health and disease, 13(1), pp. 1-10. 28
29.Greenwell, M. and Rahman, P. (2015) ‘Medicinal plants: their use in anticancer treatment’, International journal of pharmaceutical sciences and research, 6(10), pp. 4103. 29
30.Gugler, R., Leschik, M. and Dengler, H.J. (1975) ‘Disposition of quercetin in man after single oral and intravenous doses’, European journal of clinical pharmacology, 9(2), pp. 229-234. 30
31.Hanahan, D. and Weinberg, R.A. (2000) ‘The hallmarks of cancer’, Cell, 100(1), pp. 57-70. 31
32.Harwood, M., Danielewska-Nikiel, B., Borzelleca, J.F., Flamm, G.W., Williams, G.M. and Lines, T.C. (2007) ‘A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties’, Food and chemical toxicology, 45(11), pp. 2179-2205. 32
33.Hashemzaei, M., Delarami Far, A., Yari, A., Heravi, R.E., Tabrizian, K., Taghdisi, S.M., Sadegh, S.E., Tsarouhas, K., Kouretas, D. and Tzanakakis, G. (2017a) ‘Anticancer and apoptosis-inducing effects of quercetin in vitro and in vivo’, Oncology reports, 38(2), pp. 819-828. 33
36.Hassan, M., Watari, H., AbuAlmaaty, A., Ohba, Y. and Sakuragi, N. (2014) ‘Apoptosis and molecular targeting therapy in cancer’, BioMed research international, 2014. 36
37.Holliday, D.L. and Speirs, V. (2011) ‘Choosing the right cell line for breast cancer research’, Breast cancer research, 13(4), pp. 1-7. 37
38.Hopp, L. (2015) ‘Risk of bias reporting in C ochrane systematic reviews’, International journal of nursing practice, 21(5), pp. 683-686. 38
39.Huang, C., Chan, C., Chou, I., Lien, C., Hung, H. and Lee, M. (2013) ‘Quercetin induces growth arrest through activation of FOXO1 transcription factor in EGFR- overexpressing oral cancer cells’, The Journal of nutritional biochemistry, 24(9), pp. 1596-1603. 39
40.Jeong, J., An, J.Y., Kwon, Y.T., Li, L. and Lee, Y.J. (2008)’Quercetin‐induced ubiquitination and down‐regulation of Her‐2/neu’, Journal of cellular biochemistry, 105(2), pp. 585- 595. 94
41.Jørgensen, L., Paludan-Müller, A.S., Laursen, D.R., Savović, J., Boutron, I., Sterne, J.A., Higgins, J.P. and Hróbjartsson, A. (2016) ‘Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non- Cochrane reviews’, Systematic reviews, 5(1), pp. 1-13. 40
42.Kanadaswami, C., Lee, L., Lee, P.H., Hwang, J., Ke, F., Huang, Y. and Lee, M. (2005) ‘The antitumor activities of flavonoids’, In vivo, 19(5), pp. 895-909. 41
43.Kaul, T.N., Middleton Jr, E. and Ogra, P.L. (1985) ‘Antiviral effect of flavonoids on human viruses’, Journal of medical virology, 15(1), pp. 71-79. 42
44.Khorsandi, L., Orazizadeh, M., Niazvand, F., Abbaspour, M.R., Mansouri, E. and Khodadadi, A. (2017) ‘Quercetin induces apoptosis and necroptosis in MCF-7 breast cancer cells’, Bratislava Medical Journal, 118(2), pp. 123-128. 43
45.Kim, G.T., Lee, S.H. and Kim, Y.M. (2013) ‘Quercetin regulates sestrin 2-AMPK-mTOR signaling pathway and induces apoptosis via increased intracellular ROS in HCT116 colon cancer cells’, Journal of cancer prevention, 18(3), pp. 264. 44
46.Kim, H., Moon, J.Y., Ahn, K.S. and Cho, S.K. (2013)’Quercetin induces mitochondrial mediated apoptosis and protective autophagy in human glioblastoma U373MG cells’, Oxidative Medicine and Cellular Longevity, 2013. 45
47.Kim, S., Yoo, E., Woo, J., Han, S., Lee, J., Jung, S., Kim, H. and Jung, J. (2019) ‘Antitumor and apoptotic effects of quercetin on human melanoma cells involving JNK/P38 MAPK signaling activation’, European journal of pharmacology, 860, pp. 172568. 46
48.Kıyga, E., Şengelen, A., Adıgüzel, Z. and Uçar, E.Ö (2020) ‘Investigation of the role of quercetin as a heat shock protein inhibitor on apoptosis in human breast cancer cells’, Molecular biology reports, 47(7), pp. 4957-4967. 47
49.Klimisch, H.J., Andreae, M. and Tillmann, U. (1997) ‘A Systematic Approach for Evaluating the Quality of Experimental Toxicological and Ecotoxicological Data Regulatory Toxicology and Pharmacology’, . 48
50.Lee, Y., Park, S.Y., Kim, Y., Lee, W.S. and Park, O.J. (2009a) ‘AMP kinase/cyclooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin’, Experimental & molecular medicine, 41(3), pp. 201-207. 49
51.Lewis-Wambi, J.S. and Jordan, V.C. (2009) ‘Estrogen regulation of apoptosis: how can one hormone stimulate and inhibit?’, Breast cancer research, 11(3), pp. 1-12. 51
52.Lindsten, T., Ross, A.J., King, A., Zong, W., Rathmell, J.C., Shiels, H.A., Ulrich, E., Waymire, K.G., Mahar, P. and Frauwirth, K. (2000) ‘The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues’, Molecular cell, 6(6), pp. 1389-1399. 52
53.Ma, Y., Yao, C., Liu, H., Yu, F., Lin, J., Lu, K., Liao, C.,Chueh, F. and Chung, J. (2018) ‘Quercetin induced apoptosis of human oral cancer SAS cells through mitochondria and endoplasmic reticulum mediated signaling pathways’, Oncology letters, 15(6), pp. 9663-9672. 53
54.Mihaylova, M.M. and Shaw, R.J. (2011) ‘The AMPK signalling pathway coordinates cell growth, autophagy and metabolism’, Nature cell biology, 13(9), pp. 1016-1023. 54
55.Miodini, P., Fioravanti, L., Di Fronzo, G. and Cappelletti, V. (1999) ‘The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function’, British journal of cancer, 80(8), pp. 1150-1155. 55
56.Mukherjee, A. and Khuda-Bukhsh, A.R. (2015) ‘Quercetin down-regulates IL-6/STAT-3 signals to induce mitochondrial-mediated apoptosis in a nonsmall-cell lung- cancer cell line, A549’, Journal of pharmacopuncture, 18(1), pp. 19. 56
57.Murota, K., Shimizu, S., Chujo, H., Moon, J. and Terao, J. (2000) ‘Efficiency of absorption and metabolic conversion of quercetin and its glucosides in human intestinal cell line Caco-2’, Archives of Biochemistry and Biophysics, 384(2), pp. 391-397. 57
58.Nguyen, L.T., Lee, Y., Sharma, A.R., Park, J., Jagga, S., Sharma, G., Lee, S. and Nam, J. (2017) ‘Quercetin induces apoptosis and cell cycle arrest in triple-negative breast cancer cells through modulation of Foxo3a activity’, The Korean journal of physiology & pharmacology: official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 21(2), pp. 205. 58
59.Niu, G., Yin, S., Xie, S., Li, Y., Nie, D., Ma, L., Wang, X.and Wu, Y. (2011a) ‘Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and cyclooxygenase-2 pathways in human HL-60 cells’, Acta Biochim Biophys Sin, 43(1), pp. 30-37. 59
60.Noreen, Y., Serrano, G., Perera, P. and Bohlin, L. (1998) ‘Flavan-3-ols isolated from some medicinal plants inhibiting COX-1 and COX-2 catalysed prostaglandin biosynthesis’, Planta Medica, 64(06), pp. 520-524. 61
61.Ola, M.S., Nawaz, M. and Ahsan, H. (2011) ‘Role of Bcl-2 family proteins and caspases in the regulation of apoptosis’, Molecular and cellular biochemistry, 351(1), pp. 41-58. 62
62.Pfeffer, C.M. and Singh, A.T. (2018) ‘Apoptosis: a target for anticancer therapy’, International journal of molecular sciences, 19(2), pp. 448. 63
63.Pradhan, D., Pradhan, R.K., Tripathy, G. and Pradhan, S. (2015) ‘Inhibition of proteasome activity by the dietary flavonoid Quercetin associated with growth inhibition in cultured breast cancer cells and xenografts’, Journal of Young Pharmacists, 7(3), pp. 225. 64
64.Primikyri, A., Chatziathanasiadou, M.V., Karali, E., Kostaras, E., Mantzaris, M.D., Hatzimichael, E., Shin, J., Chi, S., Briasoulis, E. and Kolettas, E. (2014) ‘Direct binding of Bcl-2 family proteins by quercetin triggers its pro- apoptotic activity’, ACS chemical biology, 9(12), pp. 2737- 2741. 65
65.Priyadarsini, R.V., Murugan, R.S., Maitreyi, S., Ramalingam, K., Karunagaran, D. and 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-κB inhibition’, European journal of pharmacology, 649(1-3), pp. 84-91. 66
66.Raina, H., Soni, G., Jauhari, N., Sharma, N. and Bharadvaja, N. (2014) ‘Phytochemical importance of medicinal plants as potential sources of anticancer agents’, Turkish Journal of Botany, 38(6), pp. 1027-1035. 67
67.Rauf, A., Imran, M., Khan, I.A., ur‐Rehman, M., Gilani, S.A., Mehmood, Z. and Mubarak, M.S. (2018) ‘Anticancer potential of quercetin: A comprehensive review’, Phytotherapy Research, 32(11), pp. 2109-2130. 68
68.Ranganathan, S., Halagowder, D. and Sivasithambaram, N.D. (2015) ‘Quercetin suppresses twist to induce apoptosis in MCF-7 breast cancer cells’, PloS one, 10(10), pp. e0141370.95
69.Ravi, M., Paramesh, V., Kaviya, S.R., Anuradha, E. and Solomon, F.P. (2015) ‘3D cell culture systems: advantages and applications’, Journal of cellular physiology, 230(1), pp. 16-26. 69
70.Ravishankar, D., Rajora, A.K., Greco, F. and Osborn, H.M. (2013) ‘Flavonoids as prospective compounds for anti-cancer therapy’, The international journal of biochemistry & cell biology, 45(12), pp. 2821-2831. 70
71.Reyes-Farias, M. and Carrasco-Pozo, C. (2019) ‘The anti- cancer effect of quercetin: molecular implications in cancer metabolism’, International journal of molecular sciences, 20(13), pp. 3177. 71
72.Sadhukhan, P., Kundu, M., Chatterjee, S., Ghosh, N., Manna, P., Das, J. and Sil, P.C. (2019) ‘Targeted delivery of quercetin via pH-responsive zinc oxide nanoparticles for breast cancer therapy’, Materials science and engineering: C, 100, pp. 129- 140. 72
73.Saeidnia, S., Manayi, A. and Abdollahi, M. (2015) ‘From in vitro experiments to in vivo and clinical studies; pros and cons’, Current drug discovery technologies, 12(4), pp. 218- 224. 73
74.Schulte-Hermann, R., Grasl-Kraupp, B. and Bursch, W. (2000) ‘Dose–response and threshold effects in cytotoxicity and apoptosis’, Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 464(1), pp. 13-18. 74
75.Seo, H., Ku, J.M., Choi, H., Choi, Y.K., Woo, J., Kim, M., Kim, I., Na, C.H., Hur, H. and Jang, B. (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(1), pp. 31-42. 75
76.Stoddart, M.J. (2011) ‘Cell viability assays: introduction’, Mammalian cell viability, , pp. 1-6. 76
77.Su, Q., Peng, M., Zhang, Y., Xu, W., Darko, K.O., Tao, T., Huang, Y., Tao, X. and Yang, X. (2016) ‘Quercetin induces bladder cancer cells apoptosis by activation of AMPK signaling pathway’, American journal of cancer research, 6(2), pp. 498. 77
78.Sultan, A.S., Khalil, M.I., Sami, B.M., Alkhuriji, A.F. and Sadek, O. (2017) ‘Quercetin induces apoptosis in triple- negative breast cancer cells via inhibiting fatty acid synthase and β-catenin’, Int.J.Clin.Exp.Pathol, 10(1), pp. 156-172. 78
79.Tang, S., Deng, X., Zhou, J., Li, Q., Ge, X. and Miao, L. (2020) ‘Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects’, Biomedicine & Pharmacotherapy, 121, pp. 109604. 79
80.Teekaraman, D., Elayapillai, S.P., Viswanathan, M.P. and Jagadeesan, A. (2019) ‘Quercetin inhibits human metastatic ovarian cancer cell growth and modulates components of the intrinsic apoptotic pathway in PA-1 cell line’, Chemico- biological interactions, 300, pp. 91-100. 80
81.Theodossiou, T.A., Ali, M., Grigalavicius, M., Grallert, B., Dillard, P., Schink, K.O., Olsen, C.E., Wälchli, S., Inderberg, E.M. and Kubin, A. (2019) ‘Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT– tamoxifen hybrid therapy’, NPJ breast cancer, 5(1), pp. 1-10. 81
82.Tinoco, G., Warsch, S., Glück, S., Avancha, K. and Montero, A.J. (2013) ‘Treating breast cancer in the 21st century: emerging biological therapies’, Journal of Cancer, 4(2), pp. 117. 82
83.Tricker, A.R. (1990) ‘The effect of rounding on the significance level of certain normal test statistics’, Journal of Applied Statistics, 17(1), pp. 31-38. 83
84.Tummala, R., Lou, W., Gao, A.C. and Nadiminty, N. (2017) ‘Quercetin targets hnRNPA1 to overcome enzalutamide resistance in prostate cancer cells’, Molecular cancer therapeutics, 16(12), pp. 2770-2779. 84
85.van der Woude, H., Gliszczyńska-Świgło, A., Struijs, K., Smeets, A., Alink, G.M. and Rietjens, I.M. (2003) ‘Biphasic modulation of cell proliferation by quercetin at concentrations physiologically relevant in humans’, Cancer letters, 200(1), pp. 41-47. 85
86.Watters, A.L., Epstein, J.B. and Agulnik, M. (2011) ‘Oral complications of targeted cancer therapies: a narrative literature review’, Oral oncology, 47(6), pp. 441-448. 86
87.Xu, Z., Zhao, D., Zheng, X., Huang, B., Xia, X. and Pan, X. (2020) ‘Quercetin exerts bidirectional regulation effects on the efficacy of tamoxifen in estrogen receptor‐positive breast cancer therapy: An in vitro study’, Environmental toxicology, 35(11), pp. 1179-1193. 87
88.Yang, T., Kong, B., Gu, J., Kuang, Y., Cheng, L., Yang, W., Xia, X. and Shu, H. (2014) ‘Anti-apoptotic and anti-oxidative roles of quercetin after traumatic brain injury’, Cellular and molecular neurobiology, 34(6), pp. 797-804. 88
89.Yoshida, T., Maeda, A., Horinaka, M., Shiraishi, T., Nakata, S., Wakada, M., Yogosawa, S. and Sakai, T. (2005) ‘Quercetin induces gadd45 expression through a p53- independent pathway’, Oncology reports, 14(5), pp. 1299- 1303. 89
90.Zurrida, S. and Veronesi, U. (2015) ‘Milestones in breast cancer treatment’, The breast journal, 21(1), pp. 3-12. 90


Terms of Use/Privacy Policy/ Disclaimer/ Other Policies:
You agree that by using our site/services, you have read, understood, and agreed to be bound by all of our terms of use/privacy policy/ disclaimer/ other policies (click here for details)


CC BY 4.0
This work and its PDF file(s) are licensed under a Creative Commons Attribution 4.0 International License.