Interferon-Tau has Antiproliferative effects, Represses the Expression of E6 and E7 Oncogenes, Induces Apoptosis in Cell Lines Transformed with HPV16 and Inhibits Tumor Growth In Vivo

Herbey Oswaldo Padilla-Quirarte, Cesar Trejo-Moreno, Geny Fierros-Zarate, Jhoseline Carnalla Castañeda, Marie Palma-Irizarry, Eva Hernández-Márquez, Ana Isabel Burguete-Garcia, Oscar Peralta-Zaragoza, Vicente Madrid-Marina, Kirvis Torres-Poveda, Victor Hugo Bermúdez-Morales^✉

Division of Chronic Infection and Cancer, National Institute of Public Health, Av. Universidad 655, Cuernavaca, Morelos. Mexico, 62100.

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Citation:
Padilla-Quirarte HO, Trejo-Moreno C, Fierros-Zarate G, Castañeda JC, Palma-Irizarry M, Hernández-Márquez E, Burguete-Garcia AI, Peralta-Zaragoza O, Madrid-Marina V, Torres-Poveda K, Bermúdez-Morales VH. Interferon-Tau has Antiproliferative effects, Represses the Expression of E6 and E7 Oncogenes, Induces Apoptosis in Cell Lines Transformed with HPV16 and Inhibits Tumor Growth In Vivo. J Cancer 2016; 7(15):2231-2240. doi:10.7150/jca.15502. Available from https://www.jcancer.org/v07p2231.htm

Abstract

Interferon tau (IFN-τ) is a promising alternative antiviral and immunotherapeutic agent in a wide variety of diseases including infectious, neurodegenerative, autoimmune and cancer due to its low toxicity in comparison with other type I interferon´s. The objective of our study was established the effect of the bovine IFN-τ on human (SiHa) and murine (BMK-16/myc) cells transformed with HPV 16 and evaluates the antitumor effect in a murine tumor model HPV 16 positive. We determine that bovine IFN-τ has antiproliferative effects, pro-apoptotic activity and induces repression of viral E6 and E7 oncogenes (time- and dose-dependent) on human and murine cells transformed with HPV 16 similar to the effects of IFN-β. However, IFN-τ induces greater antiproliferative effect, apoptosis and repression of both oncogenes in BMK-16/myc cells compared to SiHa cells. The differences were explained by the presence and abundance of the type I interferon receptor (IFNAR) in each cell line. On the other hand, we treated groups of tumor-bearing mice (HPV16 positive) with IFN-τ and showed the inhibition tumor growth effect in vivo. Our finding indicates that bovine IFN-τ may be a good candidate for immunotherapy against cervical cancer.

Keywords: IFN-τ, Human papillomavirus, oncogenes, immunotherapy.