Alternative interferons and immunomodulators in the treatment of hepatitis C

Alao, Hawwa; Liang, T. Jake

doi:10.1111/liv.12402

Cited by 3 publications

(1 citation statement)

References 42 publications

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“…IFN-α has been used as a sensitizing agent for the treatment of numerous malignant human cancers such as renal cell cancer [35], gastric cancer cells [36], malignant melanoma [37], as well as hepatocellular carcinoma (HCC) [9,38], and is most often associated with the stimulation of the extrinsic apoptotic pathway [13,37]. Although the observation that IFN-α can promote cell apoptosis in cervical cancer cells has been documented before [39,40], the detailed mechanism controlling IFN-α-induced cell apoptosis is less clear.…”

Section: Discussionmentioning

confidence: 99%

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

Shi

Cao

Liu

2016

IJMS

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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.

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