T7 peptide cytotoxicity in human hepatocellular carcinoma cells is mediated by suppression of autophagy

The T7 peptide, an active fragment of full-length tumstatin [the non-collagenous 1 domain of the type IV collagen [alpha]3 chain, [alpha]3 (IV) NO], has exhibited potential antitumor effects in several types of cancer cells. However, the mechanism underlying its action against human hepatocellular c...

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Bibliographic Details
Published in:International journal of molecular medicine 2019-08, Vol.44 (2), p.523-534
Main Authors: Liu, Feng, Wang, Fuhai, Dong, Xiaofeng, Xiu, Peng, Sun, Pengfei, Li, Zhongchao, Shi, Xuetao, Zhong, Jingtao
Format: Article
Language:English
Subjects:
Amino acids
Angiogenesis
Apoptosis
Autophagy
Cancer
Cancer cells
Cancer therapies
Carcinoma
Cell cycle
Cell growth
Collagen
Cytotoxicity
Hepatitis
Hepatocellular carcinoma
Immunoglobulins
Insulin
Laboratory animals
Liver cancer
Molecular weight
Peptides
Pharmaceutical industry
Studies
Tumors
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Summary:The T7 peptide, an active fragment of full-length tumstatin [the non-collagenous 1 domain of the type IV collagen [alpha]3 chain, [alpha]3 (IV) NO], has exhibited potential antitumor effects in several types of cancer cells. However, the mechanism underlying its action against human hepatocellular carcinoma (HCC) remains unclear. The present study aimed to investigate the role of autophagy in T7 peptide-induced cytotoxicity in HCC cells in vitro and in vivo. The results revealed that the T7 peptide significantly reduced cell viability and induced cell cycle arrest in HCC cells. The T7 peptide induced apoptosis in HCC cells through upregulation of Bax, Fas, and Fas ligand, and through upregulation of the anti-apoptotic protein Bcl-2. In addition, treatment with the T7 peptide induced protective autophagy in HCC cells. Blocking autophagy by 3-methyladenineor bafilomycin A1 enhanced T7 peptide-induced apoptosis. Furthermore, co-treatment with MK-2206 (an Akt specific inhibitor) or rapamycin (an inhibitor of mTOR) enhanced T7 peptide-induced autophagy, whereas co-treatment with insulin (an activator of the Akt/mTOR signaling pathway) alleviated T7 peptide-induced autophagy, which suggested that the T7 peptide may induce autophagy activation via inhibition of the Akt/mTOR signaling pathway. Taken together, the present results demonstrated that suppression of autophagy potentiated the cytotoxic effects of the T7 peptide, and suggested that the T7 peptide may serve as a potential alternative compound for HCC therapy. Key words: hepatocellular carcinoma, T7 peptide, tumstatin, autophagy, apoptosis, Akt, mTOR
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2019.4231