Withaferin A inhibits the proliferation of gastric cancer cells by inducing G2/M cell cycle arrest and apoptosis

Abstract

Abstract. Human gastric adenocarcinoma (AGS) is one of the most common types of malignant tumor and the third-leading cause of tumor-associated mortality worldwide. Withaferin A (WA), a steroidal lactone derived from Withania somnifera, exhibits antitumor activity in a variety of cancer models. However, to the best of our knowledge, the direct effect of WA on AGS cells has not previously been determined. The present study investigated the effects of WA on the proliferation and metastatic activity of AGS cells. WA exerted a dose-dependent cytotoxic effect on AGS cells. The effect was associated with cell cycle arrest at the G2/M phase and the expression of apoptotic proteins. Additionally, WA treatment resulted in a decrease in the migration and invasion ability of the AGS cells, as demonstrated using a wound healing assay and a Boyden chamber assay. These results indicate that WA directly inhibits the proliferation and metastatic activity of gastric cancer cells, and suggest that WA may be developed as a drug for the treatment of gastric cancer.

Withaferin A triggers G2/M arrest and intrinsic apoptosis in glioblastoma cells via ATF4‐ATF3‐CHOP axis

“…Withaferin A is a bioactive compound derived from the ashwagandha plant, Withania somnifera , which has been used for safe and effective treatment of various ailments in Indian Ayurvedic medicine for centuries. Pharmacological studies of the effects of WA have shown that it is anti‐diabetic, protects liver from acetaminophen‐induced injury, prevents mammary cancer, inhibits tumour cell invasion and metastasis, induces cell cycle arrest and triggers apoptosis in breast, prostate, colorectal, non‐small cells lung and pancreatic cancer . However, the underlying mechanisms of WA’s effects on cancer are still unclear.…”

Withaferin A Induces Oxidative Stress-Mediated Apoptosis and DNA Damage in Oral Cancer Cells

“…In addition to the induction of subG1 accumulation, WFA induces G2/M arrest and a mitotic catastrophe in prostate cancer cells in terms of cell cycle analysis and western blotting for several G2/M arresting proteins (Roy et al, 2013 ). WFA also induces G2/M arrest in gastric cancer cells (Kim et al, 2017 ), osteosarcoma cells (Lv and Wang, 2015 ), and breast cancer cells (Zhang et al, 2011 ). Similar to the current study, WFA induced G2/M arrest in Ca9-22 cells at lower concentrations (1 and 2 μM) but did not present at higher concentration (3 μM) (Figure 2B ) where subG1 population (apoptosis) was gradually increased.…”

An Adaptogen: Withaferin A Ameliorates in Vitro and in Vivo Pulmonary Fibrosis by Modulating the Interplay of Fibrotic, Matricelluar Proteins, and Cytokines

“…Withaferin A is a natural steroidal lactone, rejuvenating tonifier, immunomodulator and a pre-dominant bioactive constituent obtained from Withania somnifera (Ashwagandha) which exhibits an array of potential biological activities including anti-inflammatory, anti-invasive, pro-apoptotic, and anti-fibrotic effects and is remarkably safe ( Vanden Berghe et al, 2012 ; Hahm et al, 2014 ; Madhusudan et al, 2016 ; Kim et al, 2017 ). WFA exhibits potent anti-inflammatory effect by downregulating central inflammatory mediator, nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and other cytokines which has been well-elucidated in vitro and in vivo studies ( Heyninck et al, 2014 ).…”