Binase treatment increases interferon sensitivity and apoptosis in SiHa cervical carcinoma cells by downregulating E6 and E7 human papilloma virus oncoproteins
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Vladimir A. Mitkevich1,*, Ksenia M. Burnysheva1,*, Irina Yu Petrushanko1, Alexei A. Adzhubei1, Alexey A. Schulga2, Peter M. Chumakov1 and Alexander A. Makarov1
1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
2Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117871 Moscow, Russia
*These authors have contributed equally to this work
Vladimir A. Mitkevich, email: [email protected]
Alexander A. Makarov, email: [email protected]
Keywords: cytotoxic RNase, HPV, cancer cells, apoptosis, viral oncoproteins
Received: March 22, 2017 Accepted: July 25, 2017 Published: August 10, 2017
In this study, we determined whether binase, a ribonuclease from Bacillus pumilus, increases interferon sensitivity and apoptosis in SiHa cervical cancer cells infected with high-risk human papilloma virus (HPV) strain 16. Binase treatment increased SiHa cell apoptosis in a time- and concentration-dependent manner, as determined by flow cytometry, WST tests and real time xCelligence cell index analysis. Binase-treated SiHa cells showed reduced expression of E6 and E7 viral oncoproteins and increased expression of their intracellular targets, p53 and pRb. Combined treatment with binase and IFNα2b enhanced the interferon sensitivity of HPV-positive SiHa cells. By contrast, combined treatment with binase and IFNα2b in HPV-negative C33A cervical cancer cells, which do no expess E6 and E7, elicited no changes in interferon sensitivity or p53 and pRb expression. These findings suggest binase enhances interferon sensitivity and apoptosis in HPV-positive SiHa cervical cancer cells by suppressing E6 and E7 viral protein expression.
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