Interferon-gamma induces autophagy-associated apoptosis through induction of cPLA2-dependent mitochondrial ROS generation in colorectal cancer cells.
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females and the third in males. In this work, we aim to investigate the possible anti-cancer effects of interferon-gamma (IFN-γ) in CRC cells. We observed that IFN-γ induced mitochondria-derived reactive oxygen species (ROS) production in a time-dependent manner in SW480 and HCT116 cell lines. The IFN-γ-induced mitochondrial ROS generation was dependent on the activation of cytosolic phospholipase A2 (cPLA2). In addition, a mitochondria-targeted antioxidant SS31 and/or cPLA2 inhibitor AACOCF3 abolished the IFN-γ-induced ROS production and subsequent autophagy and apoptosis. Moreover, suppression of autophagy by CQ was able to reduce IFN-γ-induced cell apoptosis. Beclin-1 gene silencing resulted in caspase-3 inactivation, decreased Bax/Bcl-2 ratio and less population of apoptotic cells. Collectively, our results suggested that IFN-γ induces autophagy-associated apoptosis in CRC cells via inducing cPLA2-dependent mitochondrial ROS production.
['Wang|Qiu-Shuang|QS|', 'Shen|Shi-Qiang|SQ|', 'Sun|Hua-Wen|HW|', 'Xing|Zhi-Xiang|ZX|', 'Yang|Hou-Lai|HL|']
D017209:Apoptosis D001343:Autophagy D000071186:Beclin-1 D045744:Cell Line, Tumor D015179:Colorectal Neoplasms D045325:HCT116 Cells D006801:Humans D007371:Interferon-gamma D008928:Mitochondria D009842:Oligopeptides D054510:Phospholipases A2, Cytosolic D017382:Reactive Oxygen Species
Interferon-gamma Apoptosis Colorectal cancer Reactive oxygen species Cytosolic phospholipase A2 Autophagy