Abstract
The inhibitor of kappa B kinase alpha (IKKα) is demonstrated to be involved in the various aspects of cancer biology, from its initiation, to progression, metastasis, and drug resistance. The aim of this study was to investigate the role of IKKα in doxorubicin (DOX)-mediated induction in apoptosis in SW-480 colon cancer cells. Cells were transfected with siRNA against IKKα and treated with DOX. MTT assay was applied to measure SW-480 cell proliferation. The mRNA levels of γ-H2AX within cells were assessed by qRT-PCR. 8-Hydroxy-2'-deoxyguanosine was measured by ELISA. The formation of intracellular reactive oxygen species (ROS) was detected by fluorometry. The antioxidant activities of some enzymes were also determined. For evaluation of apoptosis, ELISA assay was applied. IKKα silencing dramatically increased the doxorubicin cytotoxic effects. In addition, IKKα silencing substantially overexpressed γ-H2AX in SW-480 cells. Furthermore, upon IKKα silencing, the levels of ROS were elevated and the antioxidant defense system was significantly weakened. In addition, IKKα silencing led to the enhancement of apoptotic cells in doxorubicin-treated SW-480 cells. Co-treatment of IKKα and doxorubicin led to the enhanced cellular cytotoxicity via robosting ROS formation, inducing oxidative DNA damage, and decreasing cellular antioxidant defense, and finally potent apoptosis induction in cancer cell lines.
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