Piperlongumine Triggers Reactive Oxygen Species Driven Mitochondrial Dysfunction Leading to Apoptosis in Human Colon Cancer Cells

Prolonged use of conventional chemotherapy has led to adverse side effects and drug resistance, leading to therapeutic failure in colon cancer patients. An alternative therapy involving natural products with least toxicity can show promising results in cancer therapeutics. A bioactive alkaloid Piperlongumine (PIP), found in our culinary spice, exhibits potential pharmacological relevance, especially regarding its anticancer effects. This study is an original research work examining the anticancer efficacy of PIP and its related molecular mechanisms in human colon cancer cells. The results revealed that PIP induces selective cytotoxicity against colon cancer cells while inhibiting proliferation, migration and invasion. PIP also builds up reactive oxygen species (ROS) that increase the oxidative stress of the cells leading to disruption of the mitochondrial membrane and loss of mitochondrial membrane potential. In addition, PIP induces cell cycle arrest at the G₂/M phase of the cell cycle and impedes the epithelial-to-mesenchymal transition in colon cancer cells. Further, PIP-mediated elevated intracellular ROS induces DNA damage and activates the caspase-dependent apoptotic pathway in colon cancer cells. PIP also reports an anti-tumorigenic effect on the multicellular tumor spheroids of colon cancer cells. Collectively, these findings validate that PIP shows promising anticancer potential towards colon cancer cells and is a potential candidate for use in combination with existing anticancer drugs.