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Sann-Joong-Kuey-Jian-Tang induces autophagy in HepG2 cells via regulation of the phosphoinositide-3 kinase/Akt/mammalian target of rapamycin and p38 mitogen-activated protein kinase pathways

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Sann-Joong-Kuey-JianTang (SJKJT), a traditional Chinese medicine, was previously reported to induce autophagy and inhibit the proliferation of the human HepG2 hepatocellular carcinoma cell line via an extrinsic pathway. In the present study, the effects of SJKJTinduced autophagy and the cytotoxic mechanisms mediating these effects were investigated in HepG2 cells. The cytotoxicity of SJKJT in the HepG2 cells was evaluated using a 3(4,5dimethylthiazol2yl)2,5diphenyltetrazolium bromide assay. The results demonstrated that the halfmaximal inhibitory concentration of SJKJT was 2.91 mg/ml at 24 h, 1.64 mg/ml at 48 h and 1.26 mg/ml at 72 h. The results of confocal fluorescence microscopy indicated that SJKJT resulted in the accumulation of green fluorescent proteinLC3 and vacuolation of the cytoplasm. Flow cytometric analysis revealed the accumulation of acidic vesicular organelles. Furthermore, western blot analysis, used to determine the expression levels of autophagyassociated proteins, demonstrated that the HepG2 cells treated with SJKJT exhibited LC3B/LC3B conversion, increased expression levels of Beclin, Atg3 and Atg5 and reduced expression levels of p62 and decreased signaling of the phosphoinositide3 kinase/Akt/mammalian target of rapamycin and the p38 mitogenactivated protein kinase pathways. Taken together, these findings may assist in the development of novel chemotherapeutic agents for the treatment of malignant types of liver cancer.
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Document Type: Research Article

Affiliations: 1: Transplant Medicine and Surgery Research Centre, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C. 2: Department of Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan, R.O.C. 3: Institute of Biomedical Science, National Chung-Hsing University, Taichung 40227, Taiwan, R.O.C.

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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