An ideal cancer therapy specifically targets cancer cells while sparing normal
tissues. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) elicits
apoptosis by engaging its cognate death receptors (DRs—namely, DR4 and DR5. The
cancer cell-selective proapoptotic action of TRAIL is highly attractive for cancer
therapy, but clinical application of TRAIL is rather limited due to tumors’ inherent
or acquired TRAIL resistance. Combining TRAIL with agents that reverse resistance to
it has proved promising in the sensitization of TRAIL-induced apoptosis. Noteworthy,
natural compounds have already been validated as potential resources for TRAIL
sensitizers. In this review, we focus on the recently identified TRAILsensitizing
effect of tanshinones, the anticancer ingredients of the medicinal plant Salvia miltiorrhiza (Danshen in Chinese). Research from
our laboratories and others have revealed the synergy of a tanshinones-TRAIL
combination in diverse types of cancer cells through up-regulation of DR5 and/or
down-regulation of antiapoptotic proteins such as survivin. Thus, in addition to
their anticancer mechanisms, tanshinones as TRAIL sensitizers hold great potential
to be translated to TRAIL-based therapeutic modalities for combatting cancer.
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