Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry


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

General Research Article

Quercetin-Mediated Apoptosis and Cellular Senescence in Human Colon Cancer

Author(s): Serpil Özsoy*, Eda Becer, Hilal Kabadayı, Hafize S. Vatansever and Sevinç Yücecan

Volume 20 , Issue 11 , 2020

Page: [1387 - 1396] Pages: 10

DOI: 10.2174/1871520620666200408082026

Price: $65


Background: Quercetin is a flavonol from the flavonoid group of polyphenols, which positively affects human health due to its anti-cancer, anti-inflammatory, anti-microbial and cardioprotective effects. The effects of phenolic compounds, including quercetin, on programmed cell death and cellular senescence, have been the subject of research in recent years.

Objective: In this study, we aimed to investigate the effects of quercetin on cell viability, apoptosis and cellular senescence in primary (Colo-320) and metastatic (Colo-741) colon adenocarcinoma cell lines.

Methods: Cytotoxicity was analyzed via MTT assay in Colo-320 and Colo-741 cell lines. After quercetin treatment, cell ularsenescence and apoptosis were evaluated by TUNEL staining, X-Gal staining and indirect peroxidase technique for immunocytochemical analysis of related proteins such as Bax, Bcl-2, caspase-3, Hsp27, Lamin B1, p16, cyclin B1.

Results: The effective dose for inhibition of cell growth in both cell lines was determined to be 25μg/ml quercetin for 48 hours. Increased Baximmunoreactivityfollowingquercetin treatment was significant in both Colo-320 and Colo-741 cell lines, but decreased Bcl-2 immunoreactivitywas significant only in theColo-320 primary cell line. In addition, after quercetin administration, the number of TUNEL positive cells and, immunoreactivities for p16, Lamin B1 and cyclin B1 in both Colo-320 and Colo-741 cells increased.

Conclusion: Our results suggest that quercetin may only induce apoptosis in primary colon cancer cells. Furthermore, quercetin also triggered senescence in colon cancer cells, but some cells remained alive, suggesting that colon cancer cells might have escaped from senescence.

Keywords: Quercetin, polyphenol, apoptosis, cellular senescence, primary (Colo-320) colon cancer, metastatic (Colo-741) colon cancer.

Graphical Abstract
Engstrom, P.F.; Benson, A.B., III; Chen, Y.J.; Choti, M.A.; Dilawari, R.A.; Enke, C.A.; Fakih, M.G.; Fuchs, C.; Kiel, K.; Knol, J.A.; Leong, L.A.; Ludwig, K.A.; Martin, E.W., Jr; Rao, S.; Saif, M.W.; Saltz, L.; Skibber, J.M.; Venook, A.P.; Yeatman, T.J. Colon cancer clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw., 2005, 3(4), 468-491.
[] [PMID: 16038639]
Wattanathamsan, O.; Hayakawa, Y.; Pongrakhananon, V. Molecular mechanisms of natural compounds in cell death induction and sensitization to chemotherapeutic drugs in lung cancer. Phytother. Res., 2019, 33(10), 2531-2547.
[] [PMID: 31293008]
Rasouli, H.; Farzaei, M.H.; Khodarahmi, R. Polyphenols and their benefits: A review. Int. J. Food Prop., 2017, 20(Suppl. 2), 1700-1741.
Visioli, F.; De La Lastra, C.A.; Andres-Lacueva, C.; Aviram, M.; Calhau, C.; Cassano, A.; D’Archivio, M.; Faria, A.; Favé, G.; Fogliano, V.; Llorach, R.; Vitaglione, P.; Zoratti, M.; Edeas, M. Polyphenols and human health: A prospectus. Crit. Rev. Food Sci. Nutr., 2011, 51(6), 524-546.
[] [PMID: 21929330]
Massi, A.; Bortolini, O.; Ragno, D.; Bernardi, T.; Sacchetti, G.; Tacchini, M.; De Risi, C. Research progress in the modification of quercetin leading to anticancer agents. Molecules, 2017, 22(8), 1270-1297.
[] [PMID: 28758919]
D’Andrea, G. Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia, 2015, 106, 256-271.
[] [PMID: 26393898]
Khan, F.; Niaz, K.; Maqbool, F.; Ismail Hassan, F.; Abdollahi, M.; Nagulapalli Venkata, K.C.; Nabavi, S.M.; Bishayee, A. A molecular targets underlying the anticancer effects of quercetin: An update. Nutrients, 2016, 8(9), 529-548.
[] [PMID: 27589790]
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]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[] [PMID: 21376230]
Kaiser, C.A.; Krieger, M.; Lodish, H.; Berk, A. Molecular cell biology, 5th ed; Garland Science, 2007, pp. 1003-1026.
Mikuła-Pietrasik, J.; Niklas, A.; Uruski, P.; Tykarski, A.; Książek, K. Mechanisms and significance of therapy-induced and spontaneous senescence of cancer cells. Cell. Mol. Life Sci., 2020, 77(2), 213-229.
[PMID: 31414165]
Campisi, J. Aging, cellular senescence, and cancer. Annu. Rev. Physiol., 2013, 75, 685-705.
[] [PMID: 23140366]
He, S.; Sharpless, N.E. Senescence in health and disease. Cell, 2017, 169(6), 1000-1011.
[] [PMID: 28575665]
Freund, A.; Laberge, R.M.; Demaria, M.; Campisi, J. Lamin B1 loss is a senescence-associated biomarker. Mol. Biol. Cell, 2012, 23(11), 2066-2075.
[] [PMID: 22496421]
Forouzanfar, F.; Barreto, G.; Majeed, M.; Sahebkar, A. Modulatory effects of curcumin on heat shock proteins in cancer: A promising therapeutic approach. Biofactors, 2019, 45(5), 631-640.
[] [PMID: 31136038]
Lianos, G.D.; Alexiou, G.A.; Mangano, A.; Mangano, A.; Rausei, S.; Boni, L.; Dionigi, G.; Roukos, D.H. The role of heat shock proteins in cancer. Cancer Lett., 2015, 360(2), 114-118.
[] [PMID: 25721081]
Jakubowicz-Gil, J.; Rzymowska, J.; Gawron, A. Quercetin, apoptosis, heat shock. Biochem. Pharmacol., 2002, 64(11), 1591-1595.
[] [PMID: 12429348]
Vidya Priyadarsini, R.; Senthil Murugan, R.; Maitreyi, S.; Ramalingam, K.; Karunagaran, D.; Nagini, S. The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur. J. Pharmacol., 2010, 649(1-3), 84-91.
[] [PMID: 20858478]
Pan, H.C.; Jiang, Q.; Yu, Y.; Mei, J.P.; Cui, Y.K.; Zhao, W.J. Quercetin promotes cell apoptosis and inhibits the expression of MMP-9 and fibronectin via the AKT and ERK signalling pathways in human glioma cells. Neurochem. Int., 2015, 80, 60-71.
[] [PMID: 25481090]
Langner, E.; Lemieszek, M.K.; Rzeski, W. Lycopene, sulforaphane, quercetin, and curcumin applied together show improved antiproliferative potential in colon cancer cells in vitro. J. Food Biochem., 2019, 43(4) e12802
[] [PMID: 31353575]
Khan, I.; Paul, S.; Jakhar, R.; Bhardwaj, M.; Han, J.; Kang, S.C. Novel quercetin derivative TEF induces ER stress and mitochondria-mediated apoptosis in human colon cancer HCT-116 cells. Biomed. Pharmacother., 2016, 84, 789-799.
[] [PMID: 27721177]
Srivastava, N.S.; Srivastava, R.A.K. Curcumin and quercetin synergistically inhibit cancer cell proliferation in multiple cancer cells and modulate Wnt/β-catenin signaling and apoptotic pathways in A375 cells. Phytomedicine, 2019, 52, 117-128.
[] [PMID: 30599890]
Sever, R.; Brugge, J.S. Signal transduction in cancer. Cold Spring Harb. Perspect. Med., 2015, 5(4) a006098
[] [PMID: 25833940]
Khorsandi, L.; Orazizadeh, M.; Niazvand, F.; Abbaspour, M.R.; Mansouri, E.; Khodadadi, A. Quercetin induces apoptosis and necroptosis in MCF-7 breast cancer cells. Bratisl. Lek Listy, 2017, 118(2), 123-128.
[] [PMID: 28814095]
Aljofan, M.; Riethmacher, D. Anticancer activity of metformin: a systematic review of the literature. Future Sci. OA, 2019, 5(8) FSO410
[] [PMID: 31534778]
Chan, S.T.; Yang, N.C.; Huang, C.S.; Liao, J.W.; Yeh, S.L. Quercetin enhances the antitumor activity of trichostatin A through upregulation of p53 protein expression in vitro and in vivo. PLoS One, 2013, 8(1) e54255
[] [PMID: 23342112]
Chatterjee, S.; Burns, T.F. Targeting heat shock proteins in cancer: a promising therapeutic approach. Int. J. Mol. Sci., 2017, 18(9), 1978.
[] [PMID: 28914774]
Jakubowicz-Gil, J.; Langner, E.; Bądziul, D.; Wertel, I.; Rzeski, W. Silencing of Hsp27 and Hsp72 in glioma cells as a tool for programmed cell death induction upon temozolomide and quercetin treatment. Toxicol. Appl. Pharmacol., 2013, 273(3), 580-589.
[] [PMID: 24126416]
Malavolta, M.; Costarelli, L.; Giacconi, R.; Piacenza, F.; Basso, A.; Pierpaoli, E.; Marchegiani, F.; Cardelli, M.; Provinciali, M.; Mocchegiani, E. Modulators of cellular senescence: mechanisms, promises, and challenges from in vitro studies with dietary bioactive compounds. Nutr. Res., 2014, 34(12), 1017-1035.
[] [PMID: 25476190]
Liu, Y.; Tang, Z.G.; Lin, Y.; Qu, X.G.; Lv, W.; Wang, G.B.; Li, C.L. Effects of quercetin on proliferation and migration of human glioblastoma U251 cells. Biomed. Pharmacother., 2017, 92, 33-38.
[] [PMID: 28528183]
Gibellini, L.; Pinti, M.; Nasi, M.; De Biasi, S.; Roat, E.; Bertoncelli, L.; Cossarizza, A. Interfering with ROS metabolism in cancer cells: the potential role of quercetin. Cancers (Basel), 2010, 2(2), 1288-1311.
[] [PMID: 24281116]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy