Dubiusine isolated from plant induces apoptosis in human colon cancer cells.

Dubiusine, an unusual alkaloid, extracted from the leaves of the medicinal plant, for the first time and evaluated it is and cytotoxic potential in colorectal cancer (CRC). The anti-proliferative effect of the dubiusine was found to be dose-dependent with IC values of 27.95 µM, 30 µM, 30.59 µM on HTC-15, HTC-16, HT-29 cell lines respectively. Dubiusine inhibited CRC cell proliferation, induced late apoptosis, and arrested the cell cycle at the G2/M phase. Mechanistically, dubiusine down regulated the expression of anti-apoptotic proteins Bcl-2, Bcl-x and up regulated the expression of initiator and executioner caspases, that leads to apoptosis. The in silico study showed potential binding affinity of dubiusine at different caspase proteins and dynamic simulation study confirmed the structural integrity and stability of caspase-dubiusine complex.