Resveratrol induces p53 in colorectal cancer through SET7/9

Abstract

Resveratrol is one of the most promising phytoalexins for use as an anti-cancer agent, which is present in the skin of red grapes and berries. Resveratrol has been demonstrated to modulate a number of signalling pathways that are involved in carcinogenesis. In the present study, the function of resveratrol as a pro-apoptotic agent in colorectal cancer cell lines, including HCT116, CO115 and SW48, was investigated. The results revealed that resveratrol supressed cell viability. Additionally, resveratrol enhanced the expression of tumour protein p53 (p53) and p53 target genes, including Bcl2 associated X, apoptosis regulator and Bcl2 binding component 3 that have a pivotal role in p53-dependent apoptosis. Furthermore, treating cells with resveratrol upregulated SET domain containing lysine methyltransferase 7/9 (SET7/9) expression, which positively regulates p53 through its mono-methylation at lysine 372, compared with untreated cells. Furthermore, treating cells with resveratrol induced the expression of apoptotic markers including cleaved caspase-3 and poly (ADP-ribose) polymerases (PARP) compared with untreated cells. However, the genetic knockdown of SET7/9 by short hairpin RNA attenuated the resveratrol-driven overexpression of p53, cleaved caspase-3 and PARP. Collectively, these results reveal the molecular mechanisms by which resveratrol induces p53 stability in colon cancer that results in the activation of p53-mediated apoptosis.

Antimicrobial, Antioxidant, and Antiproliferative Effects of Coronilla minima: An Unexplored Botanical Species

“…The results of in silico experiments suggest the capability of resveratrol to interact with these enzymes in the micromolar range. The docking calculations were also consistent with multiple in vitro studies highlighting inhibitory effects of resveratrol and its analogs on colon cancer cell viability in both basal and pro-inflammatory conditions [36][37][38]. docking calculations were also consistent with multiple in vitro studies highlighting inhibitory effects of resveratrol and its analogs on colon cancer cell viability in both basal and pro-inflammatory conditions [36][37][38].…”

“…The results of in silico experiments suggest the capability of resveratrol to interact with these enzymes in the micromolar range. The docking calculations were also consistent with multiple in vitro studies highlighting inhibitory effects of resveratrol and its analogs on colon cancer cell viability in both basal and pro-inflammatory conditions [36][37][38].…”

“…The docking calculations were also consistent with multiple in vitro studies highlighting inhibitory effects of resveratrol and its analogs on colon cancer cell viability in both basal and pro-inflammatory conditions [36][37][38]. docking calculations were also consistent with multiple in vitro studies highlighting inhibitory effects of resveratrol and its analogs on colon cancer cell viability in both basal and pro-inflammatory conditions [36][37][38]. In order to improve our knowledge about the bio-pharmacological properties of the hydroalcoholic extract, colorimetric assays were also performed with the aim to evaluate scavenging/reducing and metal chelating properties (Table 6).…”

Polydatin Inhibits Cell Viability, Migration, and Invasion Through Suppressing the c-Myc Expression in Human Cervical Cancer

“…Increasing evidence has proven the antitumor effect of resveratrol. Notably, in human hepatocellular carcinoma cells, resveratrol suppressed invasion of cells through inhibition of tumor necrosis factor-α-mediated matrix metalloproteinase 9 (MMP9) expression (Yu et al, 2008) and caused cell cycle arrest via the activation of the p53-dependent pathway in colorectal cancer (Liu et al, 2019). These lines of evidence significantly suggested that stilbenes are promising candidates for tumor therapy.…”

Phytochemicals as Modulators of Long Non-Coding RNAs and Inhibitors of Cancer-Related Carbonic Anhydrases

“…Resveratrol (3,4′,5 tri-hydroxystilbene) (C14H12O3) is a natural polyphenol compound found in various plants and herbs, including blueberries, raspberries, mulberries, and the skin of grapes [173]. Resveratrol has anti-inflammatory and antiproliferative properties, as well as antitumor effects on various human cancers [93,174], including prostate [113,175], thyroid [176], colorectal [177,178], breast [179,180], lung [181,182], and bladder cancers [93,95,111,113,183]. Resveratrol inhibits the AR signaling pathway in prostate cancer by affecting PCGEM1 and PRNCR1 [107,108,109,110].…”