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ML-7 Amplifies the Quinocetone-Induced Cell Death Through Akt and MAPK-mediated Apoptosis on HepG2 Cell Line

Yan Zhou, Shen Zhang, Sijun Deng, Chongshan Dai, Shusheng Tang, Xiayun Yang, Daowen Li, Kena Zhao, Xilong Xiao

Toxicol Mech Methods. 2016;26(1):11-21.

PMID: 26446980

Abstract:

The study aims at evaluating the combination of the quinocetone and the ML-7 in preclinical hepatocellular carcinoma models. To this end, the effect of quinocetone and ML-7 on apoptosis induction and signaling pathways was analyzed on HepG2 cell lines. Here, we report that ML-7, in a nontoxic concentration, sensitized the HepG2 cells to quinocetone-induced cytotoxicity. Also, ML-7 profoundly enhances quinocetone-induced apoptosis in HepG2 cell line. Mechanistic investigations revealed that ML-7 and quinocetone act in concert to trigger the cleavage of caspase-8 as well as Bax/Bcl-2 ratio up-regulation and subsequent cleavage of Bid, capsases-9 and -3. Importantly, ML-7 weakened the quinocetone-induced Akt pathway activation, but strengthened the phosphorylation of p-38, ERK and JNK. Further treatment of Akt activator and p-38 inhibitor almost completely abolished the ML-7/quinocetone-induced apoptosis. In contrast, the ERK and JNK inhibitor aggravated the ML-7/quinocetone-induced apoptosis, indicating that the synergism critically depended on p-38 phosphorylation and HepG2 cells provoke Akt, ERK and JNK signaling pathways to against apoptosis. In conclusion, the rational combination of quinocetone and ML-7 presents a promising approach to trigger apoptosis in hepatocellular carcinoma, which warrants further investigation.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP110448334-A ML-7 ML-7 110448-33-4 Price
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