Resveratrol inhibits proliferation of human epidermoid carcinoma A431 cells by modulating MEK1 and AP‐1 signalling pathways

Abstract

: Resveratrol (trans‐3,4′,5‐trihydroxystilbene) is a naturally occurring polyphenolic phytoalexin found in grapes, and has been shown to inhibit the growth of various types of cancer cells. We investigated the mechanism of the antiproliferative effect of resveratrol in A431‐transformed keratinocytes harbouring mutant p53, and show that it is accompanied by G1 cell cycle arrest, which coincides with a marked inhibition of G1 cell cycle regulatory proteins, including cyclins A and D1 and cyclin‐dependent kinase (CDK)6 and p53‐independent induction of p21WAF1. Cell cycle arrest was also associated with the accumulation of hypophosphorylated Rb and p27KIP1. Resveratrol inhibited mitogen‐activated protein kinase/extracellular signal‐regulated kinase kinase (MEK)1 > extracellular signal‐regulated protein kinase (ERK)1/2 signalling, downregulated c‐Jun, and suppressed activating protein (AP)‐1 DNA‐binding and promoter activity. In addition, the inhibition of MEK1 > ERK1/2 signalling appears to be independent of retinoblastoma protein (pRb) hypophosphorylation in A431 cells, as PD098059 did not suppress pRb phosphorylation. Our results demonstrate that resveratrol affects multiple cellular targets in A431 cells, and that the downregulation of both AP‐1 and pRb contributes to its antiproliferative activity in these cells.

Mitochondrial dysfunction in resveratrol-induced apoptosis in QGY-7701 cells

“…In the present study, an MTT assay revealed that after treatment with resveratrol at a concentration of 4 µM or more, QGY-7701 viability decreases significantly. The cytotoxicity of resveratrol has been previously evaluated in different cell lines, such as U20S (human osteosarcoma cell line) (Liu et al, 2012), 786-0 (human renal cancer cell line) (Yang et al, 2011), and A431 (human epidermoid carcinoma cells) (Kim et al, 2006). The results of these studies indicate that resveratrol indeed has cytotoxicity.…”

Evaluation of Resveratrol and Piceatannol Cytotoxicity in Macrophages, T Cells, and Skin Cells

“…Similarly, the cytotoxic potential of resveratrol towards skin cells is at present unclear. However, while evidence exists to suggest an antiproliferative activity of this compound on certain types of skin cells in vitro (26)(27)(28), data generated from in vivo studies have not been as conclusive (29).…”

Ultraviolet A exposure induces reversible disruption of gap junction intercellular communication in lens epithelial cells

“…The p38 MAPK signaling pathway allows cells to interpret a wide range of external signals and respond appropriately by generating a plethora of different biological effects (30). Phosphorylation and activation of p38 kinase is related to a cellular stress condition and its activity contributes to the regulation of growth arrest, differentiation and apoptosis in response to a variety of cellular stresses (31,32). Previously, UVA-induced GJIc down-regulation in human keratinocytes has been reported to be involved in p38 activation-dependent cx43 phosphorylation and degradation (19).…”