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Cucurbitacin-I Induces Hypertrophy in H9c2 Cardiomyoblasts Through Activation of Autophagy via MEK/ERK1/2 Signaling Pathway

Cucurbitacin-I Induces Hypertrophy in H9c2 Cardiomyoblasts Through Activation of Autophagy via MEK/ERK1/2 Signaling Pathway

Yao Wu, Hongying Chen, Ruli Li, Xiaoxiao Wang, He Li, Juanjuan Xin, Zhiqiang Liu, Sisi Wu, Wei Jiang, Ling Zhu

Toxicol Lett. 2016 Dec 15;264:87-98.

PMID: 27836799

Abstract:

Cucurbitacin-I, a natural triterpenoids initially identified in medicinal plants, shows a potent anticancer effect on a variety of cancer cell types. Nevertheless, the cardiotoxicity of cucurbitacin-I has not heretofore been reported. In this study, the mechanisms of cucurbitacin-I-induced cardiotoxicity were examined by investigating the role of MAPK-autophagy-dependent pathways. After being treated with 0.1-0.3μM cucurbitacin-I for 48h, H9c2 cells showed a gradual decrease in the cell viabilities, a gradual increase in cell size, and mRNA expression of ANP and BNP (cardiac hypertrophic markers). Cucurbitacin-I concentration-dependent apoptosis of H9c2 cells was also observed. The increased apoptosis of H9c2 cells was paralleling with the gradually strong autophagy levels. Furthermore, an autophagy inhibitor, 3-MA, was used to block the cucurbitacin-I-stirred autophagy, and then the hypertrophy and apoptosis induced by 0.3μM cucurbitacin-I were significantly attenuated. In addition, cucurbitacin-I exposure also activated the MAPK signaling pathways, including ERK1/2, JNK, and p38 kinases. Interestingly, only the ERK inhibitor U0126, but not the JNK inhibitor SP600125 and p38 MAPK inhibitor SB203580, weakened the induction of 0.3μM cucurbitacin-I in hypertrophy, autophagy and apoptosis. Our findings suggest that cucurbitacin-I can increase the autophagy levels of H9c2 cells, most likely, through the activation of an ERK-autophagy dependent pathway, which results in the hypertrophy and apoptosis of cardiomyocytes.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2222073-A	Cucurbitacin I		2222-07-3	Price

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