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Int. J. Mol. Sci. 2016, 17(11), 1832; doi:10.3390/ijms17111832

Interferon α Induces the Apoptosis of Cervical Cancer HeLa Cells by Activating both the Intrinsic Mitochondrial Pathway and Endoplasmic Reticulum Stress-Induced Pathway

1
Department of Microbiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
2
Beijing Institute of Biotechnology, Academy of Military Medical Sciences, 27 Taiping Rd., Haidian District, Beijing 100850, China
*
Author to whom correspondence should be addressed.
Academic Editor: Anthony Lemarié
Received: 29 July 2016 / Revised: 14 October 2016 / Accepted: 27 October 2016 / Published: 2 November 2016
(This article belongs to the Collection Programmed Cell Death and Apoptosis)
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Abstract

The interferon α (IFN-α) has been often used as a sensitizing agent for the treatment of various malignancies such as hepatocellular carcinoma, malignant melanoma, and renal cell cancer by promoting the apoptosis of thesetumor cell types. However, the effect of IFN-α on cervical cancer remains unknown. In this study, HeLa cells were used as a testing model for the treatment of IFN-α on cervical cancer. The results indicate that IFN-α markedly inhibits the proliferation and induces the apoptosis of HeLa cells. The activation of caspase 3, the up-regulation of both Bim and cleaved poly (ADP-ribose) polymerase (PARP) 1, the down-regulation of Bcl-xL, as well as the release of cytochrome c from mitochondria were significantly induced upon IFN-α treatment, indicating that the intrinsic apoptotic pathway could be activated by IFN-α treatment. In addition, caspase 4—which is involved in the endoplasmic reticulum (ER) stress-induced apoptosis—was activated in response to IFN-α treatment. Knocking down caspase 4 by small interfering RNA (siRNA) markedly reduced the IFN-α-mediated cell apoptosis. However, no significant changes in the expressions of caspases 8 and 10 were observed upon IFN-α treatment, indicating that the apoptosis caused by IFN-α might be independent of the extrinsic apoptotic pathway. These findings suggest that IFN-α may possess anti-cervical cancer capacity by activating cell apoptosis via the intrinsic mitochondrial pathway and caspase-4-related ER stress-induced pathway. View Full-Text
Keywords: interferon α (IFN-α); apoptosis; HeLa cell; intrinsic mitochondrial pathway; ER stress; caspase 4 interferon α (IFN-α); apoptosis; HeLa cell; intrinsic mitochondrial pathway; ER stress; caspase 4
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Shi, W.-Y.; Cao, C.; Liu, L. Interferon α Induces the Apoptosis of Cervical Cancer HeLa Cells by Activating both the Intrinsic Mitochondrial Pathway and Endoplasmic Reticulum Stress-Induced Pathway. Int. J. Mol. Sci. 2016, 17, 1832.

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