Quercetin-Mediated Apoptosis and Cellular Senescence in Human Colon Cancer

Abstract

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, cellular senescence 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 Bax immunoreactivity following quercetin treatment was significant in both Colo-320 and Colo-741 cell lines, but decreased Bcl-2 immunoreactivity was significant only in the Colo-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.

Rutin Exerts Cytotoxic and Senescence-Inducing Properties in Human Melanoma Cells

“…The most prominent results were acquired at the highest concentration of 50 µM ( Figure 6 ) when specific senescence features such as increased cell size, and elevated senescent-associated beta-galactosidase (SA-β-gal) expression [ 44 ] highlighted by a dark coloration within the cell cytoplasm were detected. Our results are endorsed by previous studies that reported the capacity of several natural bioactive compounds (e.g., curcumin, quercetin) to force cancer cells to undergo senescence in vitro [ 45 , 46 , 47 ]. Multiple mechanistic pathways have been attributed to the pro-senescence effect of natural polyphenols in cancer cells, including modulation of tumor suppressor or oncogene gene expression, DDR (DNA damage response) activation, ROS generation, promotion of endoplasmic reticulum (ER) stress, and regulation of epigenetics [ 48 ].…”

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…Quercetin treatment reduced cell viability and induced apoptosis in primary and metastatic colon adenocarcinoma cell lines [407]. Quercetin dose-dependently suppressed HGF-and TGFα-induced migration of hepatocellular carcinoma cells by inhibiting the signaling pathway of AKT, but not p38 MAPK [413].…”

Quercetin Reverses Cardiac Systolic Dysfunction in Mice Fed with a High‐Fat Diet: Role of Angiogenesis

“…hyperlipidemic rats, Q pretreatment before I/R injury increased myocardial infarct size and release of lactate dehydrogenase and creatine kinase-MB [32]. On the other hand, Q upregulated p16 expression in colon adenocarcinoma cell lines, causing cell cycle arrest and thereby preventing proliferation of cancer cells [33]. Speculatively, the increase of p16 in HQ might arrest fibroblast cells proliferation and thereby decrease cardiac fibrosis.…”