Open Access

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

  • Authors:
    • Feng Liu
    • Fuhai Wang
    • Xiaofeng Dong
    • Peng Xiu
    • Pengfei Sun
    • Zhongchao Li
    • Xuetao Shi
    • Jingtao Zhong
  • View Affiliations

  • Published online on: June 6, 2019     https://doi.org/10.3892/ijmm.2019.4231
  • Pages: 523-534
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The T7 peptide, an active fragment of full‑length tumstatin [the non‑collagenous 1 domain of the type IV collagen α3 chain, α3 (IV) NC1], 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.

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August 2019
Volume 44 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Liu, F., Wang, F., Dong, X., Xiu, P., Sun, P., Li, Z. ... Zhong, J. (2019). T7 peptide cytotoxicity in human hepatocellular carcinoma cells is mediated by suppression of autophagy. International Journal of Molecular Medicine, 44, 523-534. https://doi.org/10.3892/ijmm.2019.4231
MLA
Liu, F., Wang, F., Dong, X., Xiu, P., Sun, P., Li, Z., Shi, X., Zhong, J."T7 peptide cytotoxicity in human hepatocellular carcinoma cells is mediated by suppression of autophagy". International Journal of Molecular Medicine 44.2 (2019): 523-534.
Chicago
Liu, F., Wang, F., Dong, X., Xiu, P., Sun, P., Li, Z., Shi, X., Zhong, J."T7 peptide cytotoxicity in human hepatocellular carcinoma cells is mediated by suppression of autophagy". International Journal of Molecular Medicine 44, no. 2 (2019): 523-534. https://doi.org/10.3892/ijmm.2019.4231