Sesquiterpene lactones as drugs with multiple targets in cancer treatment

Sesquiterpene lactones (SLs) constitute a large and diverse group of biologically active plant compounds that possess anti-inflammatory and antitumor activity. The subclass germacranolides is one of the major groups of SLs. It includes parthenolide, a highly cytotoxic SL that is being tested in clinical trials as an anti-cancer agent. In this review, we focus on SL antitumor activity related to cell-cycle arrest, differentiation, apoptosis induction through the intrinsic pathway, and sensitization of the extrinsic pathway. We also address the regression of tumors in response to cotreatment with conventional chemotherapeutics. We review the nuclear factor-κB-targeted anti-inflammatory activity in vitro and in vivo and relate it to the SL structural features involved in the molecular mechanisms. It is obvious that SLs are emerging as promising anticancer agents, but more investigations are required to fully understand the molecular mechanisms of known SLs in different cell death modalities and how these mechanisms contribute toward the potent antitumor and anti-inflammatory activities of SLs.