In vitro and in vivo anticancer efficacy of the combination of actinomycin D and resveratrol

Actinomycin D (Act D) was the first FDA-approved anticancer antibiotic. However, its widespread application was hindered by dose-limiting toxicities. In the current study, we investigated the in vitro and in vivo anticancer efficacy of the combination of Act D with resveratrol. We found that the combination of Act D and resveratrol has better in vitro efficacy than any of the single agent. We also explored the underlying mechanism by investigating the activation of the p53 pathway. Consistent with the cell growth inhibition, Act D, resveratrol, and their combination activated p53 and induced the expression of <i>p21, PUMA</i>, and <i>GDF15</i> mRNA and proteins. The combination had better effects than any of the single agents alone. Ablation of p53 significantly protected cells and confirmed p53-dependent expression of these genes. Finally, we investigated the in vivo efficacy of these agents and their combination using xenograft model. Act D, resveratrol, and their combination significantly inhibited the growth of xenografts. The in vivo efficacy was further supported by Ki-67 expression in tumor tissues. Taken together, our findings demonstrated that although the combination of Act D and resveratrol showed better efficacy in vitro than any of the single agent, the in vivo efficacy was not improved.