Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

General Research Article

Is Quercetin Beneficial for Colon Cancer? A Cell Culture Study, Using the Apoptosis Pathways

Author(s): Meltem Özgöçmen*, Dilek Bayram, İlkay Armağan, Gülçin Yavuz Türel, Murat Sevimli and Nurgül Şenol

Volume 22, Issue 1, 2022

Published on: 24 June, 2021

Page: [193 - 200] Pages: 8

DOI: 10.2174/1871520621666210624110547

Price: $65

Abstract

Background: Quercetin (QCT) is a dietary flavonoid with many beneficial effects (e.g., antioxidant, antiaging, antidiabetic, antifungal effects, and regulation of gastrointestinal motor activity in human); furthermore, it induces apoptosis, cell cycle arrest, and differentiation.

Objective: The apoptotic effects of OCT were investigated on SW480 human colon cancer cell lines in monolayer and spheroid cultures.

Methods: Quercetin (40–200 μM) was applied, and Inhibitory Concentration (IC50) doses were determined for three time intervals (24, 48, and 72 h). The effective dose was determined and applied for analyses, including staining with BrdU to investigate cell proliferation, terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) to investigate apoptosis, and caspase-3 and Apoptosis Inducing Factor (AIF) to investigate caspase-dependent or independent apoptotic pathways.

Results: The effective dose of QCT was determined to be 200 μM and was found to induce apoptosis and inhibit cell proliferation at 24, 48, and 72 h,both in 2D and 3D cultures. Significant increases were observed in both caspase-3 and AIF staining, but cells showed greater caspase-3 staining compared with AIF staining at all time intervals (p<0.05).

Conclusion: The QCT treatment groups showed more cell death and less cell growth compared with the untreated control groups in both 2D and 3D cultures of SW480 cell lines. The results suggest that quercetin induces apoptosis, inhibits cell proliferation, and has a protective role against colon cancer. However, further studies are needed to clarify its mechanism of action.

Keywords: AIF, caspase 3, monolayer culture, quercetin, spheroid culture, SW480.

Graphical Abstract
[1]
Xu, G.; Shi, H.; Ren, L.; Gou, H.; Gong, D.; Gao, X.; Huang, N. Enhancing the anti-colon cancer activity of quercetin by self-assembled micelles. Int. J. Nanomedicine, 2015, 10, 2051-2063.
[PMID: 25844036]
[2]
Zhang, X-A.; Zhang, S.; Yin, Q.; Zhang, J. Quercetin induces human colon cancer cells apoptosis by inhibiting the nuclear factor-kappa B Pathway. Pharmacogn. Mag., 2015, 11(42), 404-409.
[http://dx.doi.org/10.4103/0973-1296.153096] [PMID: 25829782]
[3]
Yang, L.; Liu, Y.; Wang, M.; Qian, Y.; Dong, X.; Gu, H.; Wang, H.; Guo, S.; Hisamitsu, T. Quercetin-induced apoptosis of HT-29 colon cancer cellsviainhibition of the Akt-CSN6-Myc signaling axis. Mol. Med. Rep., 2016, 14(5), 4559-4566.
[http://dx.doi.org/10.3892/mmr.2016.5818] [PMID: 27748879]
[4]
Eldahshan, O.A.; Abdel-Daim, M.M. Phytochemical study, cytotoxic, analgesic, antipyretic and anti-inflammatory activities of Strychnos nux-vomica. Cytotechnology, 2015, 67(5), 831-844.
[http://dx.doi.org/10.1007/s10616-014-9723-2] [PMID: 24711053]
[5]
Mouat, M.F.; Kolli, K.; Orlando, R.; Hargrove, J.L.; Grider, A. The effects of quercetin on SW480 human colon carcinoma cells: a proteomic study. Nutr. J., 2005, 4, 11.
[http://dx.doi.org/10.1186/1475-2891-4-11] [PMID: 15748282]
[6]
He, B.; Wang, X.; Shi, H.S.; Xiao, W.J.; Zhang, J.; Mu, B.; Mao, Y.Q.; Wang, W.; Wang, Y.S. Quercetin liposome sensitizes colon carcinoma to thermotherapy and thermochemotherapy in mice models. Integr. Cancer Ther., 2013, 12(3), 264-270.
[http://dx.doi.org/10.1177/1534735412446863] [PMID: 22740083]
[7]
Darband, S.G.; Kaviani, M.; Yousefi, B.; Sadighparvar, S.; Pakdel, F.G.; Attari, J.A.; Mohebbi, I.; Naderi, S.; Majidinia, M. Quercetin: A functional dietary flavonoid with potential chemo-preventive properties in colorectal cancer. J. Cell. Physiol., 2018, 233(9), 6544-6560.
[http://dx.doi.org/10.1002/jcp.26595] [PMID: 29663361]
[8]
Omidifar, N.; Nili-Ahmadabadi, A.; Gholami, A.; Dastan, D.; Ahmadimoghaddam, D.; Nili-Ahmadabadi, H. Biochemical and histological evidence on the protective effects of allium hirtifolium boiss (persian shallot) as an herbal supplement in cadmium-induced hepatotoxicity. Evid. Based Complement. Alternat. Med., 2020, 2020,
[9]
Zeng, Y.; Shen, Z.; Gu, W.; Wu, M. Bioinformatics analysis to identify action targets in NCI-N87 gastric cancer cells exposed to quercetin. Pharm. Biol., 2018, 56(1), 393-398.
[http://dx.doi.org/10.1080/13880209.2018.1493610] [PMID: 30266078]
[10]
Pampaloni, B.; Palmini, G.; Mavilia, C.; Zonefrati, R.; Tanini, A.; Brandi, M.L. in vitro effects of polyphenols on colorectal cancer cells. World J. Gastrointest. Oncol., 2014, 6(8), 289-300.
[http://dx.doi.org/10.4251/wjgo.v6.i8.289] [PMID: 25132926]
[11]
Rha, C.S.; Jeong, H.W.; Park, S.; Lee, S.; Jung, Y.S.; Kim, D.O. Antioxidative, anti-inflammatory, and anticancer effects of purified flavonol glycosides and aglycones in green tea. Antioxidants (Basel, Switzerland), 2019, 8(8), 278.
[12]
Amado, N.G.; Predes, D.; Fonseca, B.F.; Cerqueira, D.M.; Reis, A.H.; Dudenhoeffer, A.C.; Borges, H.L.; Mendes, F.A.; Abreu, J.G. Isoquercitrin suppresses colon cancer cell growth in vitro by targeting the Wnt/β-catenin signaling pathway. J. Biol. Chem., 2014, 289(51), 35456-35467.
[http://dx.doi.org/10.1074/jbc.M114.621599] [PMID: 25359775]
[13]
Ashkenazi, A. Targeting the extrinsic apoptosis pathway in cancer. Cytokine Growth Factor Rev., 2008, 19(3-4), 325-331.
[http://dx.doi.org/10.1016/j.cytogfr.2008.04.001] [PMID: 18495520]
[14]
Wong, R.S. Apoptosis in cancer: from pathogenesis to treatment. J. Exp. Clin. Cancer Res. CR (East Lansing Mich.), 2011, 30(1), 87.
[15]
Sayers, T.J. Targeting the extrinsic apoptosis signaling pathway for cancer therapy. Cancer Immunol. Immunother., 2011, 60(8), 1173-1180.
[http://dx.doi.org/10.1007/s00262-011-1008-4] [PMID: 21626033]
[16]
Cincin, Z.B.; Unlu, M.; Kiran, B.; Bireller, E.S.; Baran, Y.; Cakmakoglu, B. Apoptotic effects of quercitrin on DLD-1 colon cancer cell line. Pathol. Oncol. Res., 2015, 21(2), 333-338.
[http://dx.doi.org/10.1007/s12253-014-9825-3] [PMID: 25096395]
[17]
Hashemzaei, M.; Delarami Far, A.; Yari, A.; Heravi, R.E.; Tabrizian, K.; Taghdisi, S.M.; Sadegh, S.E.; Tsarouhas, K.; Kouretas, D.; Tzanakakis, G.; Nikitovic, D.; Anisimov, N.Y.; Spandidos, D.A.; Tsatsakis, A.M.; Rezaee, R. Anticancer and apoptosis inducing effects of quercetin in vitro and in vivo. Oncol. Rep., 2017, 38(2), 819-828.
[http://dx.doi.org/10.3892/or.2017.5766] [PMID: 28677813]
[18]
Shafabakhsh, R.; Asemi, Z. Quercetin: a natural compound for ovarian cancer treatment. J. Ovarian Res., 2019, 12(1), 55.
[http://dx.doi.org/10.1186/s13048-019-0530-4] [PMID: 31202269]
[19]
Reyes-Farias, M.; Carrasco-Pozo, C. The anti-cancer effect of quercetin: molecular implications in cancer metabolism. Int. J. Mol. Sci., 2019, 20(13), 3177.
[http://dx.doi.org/10.3390/ijms20133177] [PMID: 31261749]
[20]
Gokhale, J.P.; Mahajan, H.S.; Surana, S.J. Quercetin loaded nanoemulsion-based gel for rheumatoid arthritis: in vivo and in vitro studies. Biomed. Pharmacother., 2019, 112108622
[http://dx.doi.org/10.1016/j.biopha.2019.108622] [PMID: 30797146]
[21]
Lan, H.; Hong, W.; Fan, P.; Qian, D.; Zhu, J.; Bai, B. Quercetin inhibits cell migration and invasion in human osteosarcoma cells. Cell. Physiol. Biochem., 2017, 43(2), 553-567.
[http://dx.doi.org/10.1159/000480528] [PMID: 28965117]
[22]
Liu, Q.; Yang, X.; Sun, J.; Yu, F.; Zhang, H.; Gao, J.; Zheng, A. Size-dependent biological effects of quercetin nanocrystals. Molecules, 2019, 24(7), 1438.
[http://dx.doi.org/10.3390/molecules24071438] [PMID: 30979064]
[23]
Godugu, C.; Patel, A.R.; Desai, U.; Andey, T.; Sams, A.; Singh, M. AlgiMatrix™ based 3D cell culture system as an in-vitro tumor model for anticancer studies. PLoS One, 2013, 8(1)e53708
[http://dx.doi.org/10.1371/journal.pone.0053708] [PMID: 23349734]
[24]
Bayram, D.; Çetin, E.S.; Kara, M.; Özgöçmen, M.; Candan, I.A. The apoptotic effects of silibinin on MDA-MB-231 and MCF-7 human breast carcinoma cells. Hum. Exp. Toxicol., 2017, 36(6), 573-586.
[http://dx.doi.org/10.1177/0960327116658105] [PMID: 27402681]
[25]
Bayram, D.; Armagan, İ.; Özgöcmen, M.; Senol, N.; Calapoglu, M. Determination of apoptotic effect of juglone on human bladder cancer TCC-SUP and RT-4 cells: An in vitro study. J. Environ. Pathol. Toxicol. Oncol., 2018, 37(2), 173-181.
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2018025226] [PMID: 30055552]
[26]
Chien, S-Y.; Wu, Y-C.; Chung, J-G.; Yang, J-S.; Lu, H-F.; Tsou, M-F.; Wood, W.G.; Kuo, S-J.; Chen, D-R. Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells. Hum. Exp. Toxicol., 2009, 28(8), 493-503.
[http://dx.doi.org/10.1177/0960327109107002] [PMID: 19755441]
[27]
Chan, C-Y.; Lien, C-H.; Lee, M-F.; Huang, C-Y. Quercetin suppresses cellular migration and invasion in human head and neck squamous cell carcinoma (HNSCC). Biomedicine (Taipei), 2016, 6(3), 15.
[http://dx.doi.org/10.7603/s40681-016-0015-3] [PMID: 27510965]
[28]
Özsoy, S.; Becer, E.; Kabadayı, H.; Vatansever, H.S.; Yücecan, S. Quercetin-mediated apoptosis and cellular senescence in human colon cancer. Anticancer. Agents Med. Chem., 2020, 20(11), 1387-1396.
[http://dx.doi.org/10.2174/1871520620666200408082026] [PMID: 32268873]
[29]
Niu, G.; Yin, S.; Xie, S.; Li, Y.; Nie, D.; Ma, L.; Wang, X.; Wu, Y. Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and cyclooxygenase-2 pathways in human HL-60 cells. Acta Biochim. Biophys. Sin. (Shanghai), 2011, 43(1), 30-37.
[http://dx.doi.org/10.1093/abbs/gmq107] [PMID: 21173056]
[30]
Psahoulia, F.H.; Drosopoulos, K.G.; Doubravska, L.; Andera, L.; Pintzas, A. Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts. Mol. Cancer Ther., 2007, 6(9), 2591-2599.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-0001] [PMID: 17876056]
[31]
Lee, Y.K.; Park, S.Y.; Kim, Y.M.; Lee, W.S.; Park, O.J. AMP kinase/cyclooxygenase-2 pathway regulates proliferation and apoptosis of cancer cells treated with quercetin. Exp. Mol. Med., 2009, 41(3), 201-207.
[http://dx.doi.org/10.3858/emm.2009.41.3.023] [PMID: 19293639]
[32]
Liu, H.; Zhou, M. Antitumor effect of Quercetin on Y79 retinoblastoma cellsviaactivation of JNK and p38 MAPK pathways.BMC Complement. Altern. Med., 2017, 17(1), 531.,
[http://dx.doi.org/10.1186/s12906-017-2023-6] [PMID: 29237430]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy