Fig. 3.

The anticancer mechanism of lycorine. A. Apoptosis induction by lycorine. Lycorine targets Bcl-2 pro-apoptotic family protein and downregulates them to induce intrinsic apoptosis in cells. It can also promote extrinsic apoptosis cascade by upregulating death legands. B. Cell cycle inhibition. Lycorine is suggested to target cell cycle inhibitor p21 to induce cell cycle arrest in cancer cells. C. Lycorine induced program necrosis is associated with increased ROS generation, DNA damage and ATP depletion. D. Lycorine inhibits autophagy in cancer cells. It can promote proteasomal degradation of important autophagy regulator HMGB1 and thereby sequestrates Beclin1 with Bcl-2 resulting in autophagy inhibition. E. The proposed combinatory anticancer mechanism of lycorine. Lycorine inhibits autophagy, causing accumulation of damaged mitochondria that lead to increased generation of ROS. These ROS may induce DNA damage and at the same time, cells with damaged-DNA may arrest their cell cycle at a specific checkpoint. The populations of cells with arrested cell cycle then commit death in a programmed manner either by apoptosis or by necrosis. Experimental detail is required to verify this postulation (LYC; Lycorine).