Poly (I:C) transfection induces mitochondrial-mediated apoptosis in cervical cancer.

Polyinosinic acid:polycytidylic acid, known as poly (I:C), is an analogue of double-stranded RNA, which exhibits direct antitumor effects against several types of cancer. The present study aimed to evaluate the role of poly (I:C) in the apoptosis of cervical cancer cells. The HeLa human cervical cancer cell line was used in the present study, and cell apoptosis was determined following poly (I:C) transfection. Furthermore, the mRNA levels of interferon (IFN)-, the production of reactive oxygen species (ROS), DNA damage, mitochondrial membrane potential (m) and the release of cytochrome c, as well as caspase activation, were determined. The effect of IFN- on poly (I:C) transfection-mediated apoptosis was also examined by IFN- knockdown. The results showed that poly (I:C) transfection markedly induced HeLa apoptosis, increased the protein levels of pro-apoptotic B cell lymphoma-2 (Bcl-2)-associated X protein (Bax) and BH3 interacting-domain death agonist (Bid), and suppressed the protein expression levels of anti-apoptotic Bcl-2 and Survivin. However, poly (I:C) transfection increased the mRNA levels of IFN-, induced ROS production and increased the levels of phosphorylated H2A.X, an indicator of DNA damage. In addition, poly (I:C) transfection decreased m, triggered the release of cytochrome c from the mitochondria to the cytosol, and induced caspase-9 and -3 activation. IFN- knockdown decreased the poly (I:C)-induced production of ROS and DNA damage, restored m and cytochrome c release, and suppressed caspase-9 and -3 activation, thereby suppressing poly (I:C)-mediated apoptosis in the HeLa cells. Together, the results of the present study demonstrated that poly (I:C) transfection induced IFN-, contributing to ROS production, DNA damage, and caspase-9 and -3 activation in the HeLa cervical cancer cell line, leading to mitochondrial-mediated apoptosis.