Combinatorial strategies for cancer eradication by silibinin and cytotoxic agents: efficacy and mechanisms

In an effort to develop effective alternative strategies that increase the therapeutic efficacy and minimize the systemic toxicity of chemotherapeutic agents, more efforts are being directed towards the investigation of dietary supplements and other phytotherapeutic agents for their synergistic efficacy in combination with anticancer drugs. One such agent is silibinin, which has shown promising chemopreventive and anticancer effects in various in vitro and in vivo studies. The present review summarizes the effects of the combination of silibinin and chemotherapeutic drugs on the growth inhibition, cell cycle regulation, and apoptosis induction in prostate, breast, and lung cancer systems. Together, the results indicate a synergistic effect of silibinin on growth inhibition, reversal of chemoresistance, apoptosis induction, and a strong increase in G2–M checkpoint arrest when given in combination with these drugs. These results are highly significant with respect to the combined chemotherapy approach, wherein the criteria for combination is that the response has to be synergistic and that the drugs should not share common mechanisms of resistance and not overlap in their major side-effects.