Figure 7.

A schematic illustration of proposed mechanism for anti-myeloma activity of lycorine. HMGB1 acts as an important mediator of autophagy. It can directly bind with Beclin-1 or activate MEK-ERK to free Beclin-1 from Bcl-2 and initiate autophagy which facilitates cell survival and confers resistance. Lycorine is suggested to mediate HMGB1 degradation through proteasome pathway, inhibits MEK-ERK activation and thereby increase Bcl-2-Beclin-1 interaction. As a result causes inhibition of pro-survival autophagy and leads to cell death.