Antitumor activity of glycyrol via induction of cell cycle arrest, apoptosis and defective autophagy.
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| Abstract |
Glycyrol is a coumestan isolated from Glycyrrhiza uralensis and synthesized to use. In this study, the antitumor activity and the underlying mechanism of glycyrol were evaluated in vitro and in vivo. It was shown that glycyrol induced cell death associated with apoptosis and autophagy as evidenced by morphological changes in AGS and HCT 116 cells. The apoptosis-inducing effect was characterized by increase in ratio of sub-G1 phase, poly (ADP-ribose) polymerase-1 (PARP-1) cleavage and caspase-3 activation. Mechanistic studies showed that glycyrol induced G0/G1 phase cell cycle arrest as indicated by increase in p21. Furthermore, c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinases (MAPKs) activation induced caspase-dependent apoptosis accompanied by adenosine monophosphate-activated protein kinase (AMPK) activation. Defective autophagy was triggered, which stopped the autophagic flux by the slowing of lysosomal degradation. In addition, glycyrol suppressed tumor growth in a nude mouse tumor xenograft model bearing HCT 116 cells. Taken together, glycyrol is demonstrated to have antitumor activity, and might potentially serve as potential candidate for cancer therapy.
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| Authors | Mei-Ying Xu, Yeong Shik Kim |
| Journal | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 74 Pg. 311-9 (Dec 2014) ISSN: 1873-6351 [Electronic] England |
| PMID | 25445757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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