Xanthatin mediates G₂/M cell cycle arrest, autophagy and apoptosis via ROS/XIAP signaling in human colon cancer cells

Abstract

Xanthatin is a natural plant bicyclic sesquiterpene lactone extracted from Xanthium plants (Asteraceae). In the present study, we demonstrated for the first time that Xanthatin inhibited cell proliferation and mediated G₂/M phase arrest in human colon cancer cells. Xanthatin also activated caspase and mediated apoptosis in these cells. Concomitantly, Xanthatin triggered cell autophagic response. We found down-regulation of X-linked inhibitor of apoptosis protein (XIAP) contribute to the induction of apoptosis and autophagy. Moreover, reactive oxygen species (ROS) production was triggered upon exposure to Xanthatin in colon cancer cells. ROS inhibitor N-acetylcysteine (NAC) significantly reversed Xanthatin-mediated XIAP down-regulation, G₂/M phase arrest, apoptosis and autophagosome accumulation. In summary, our findings demonstrated that Xanthatin caused G₂/M phase arrest and mediated apoptosis and autophagy through ROS/XIAP in human colon cancer cells. We provided molecular bases for developing Xanthatin as a promising antitumor candidate for colon cancer therapy.

Abbreviations
ROS	=	reactive oxygen species
DMSO	=	dimethyl sulfoxide
5-FU	=	5-Fluorouracil
3-MA	=	3-Methyladenine
DCFH-DA	=	2’7’-dichlorfluorescein-diacetate
NAC	=	N-acetylcysteine
XIAP	=	X-linked inhibitor of apoptosis protein

Keywords:

• Xanthatin
• cell cycle
• apoptosis
• autophagy
• XIAP
• colon cancer

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was co-supported by the National Natural Science Foundation of China (Program No. 81603339, 81602344) and Natural Science Foundation of Anhui Province (Program No. 1708085QH175).