REVIEW ARTICLESesquiterpene lactones as drugs with multiple targets in cancer treatment focus on parthenolideOrofino Kreuger, Maria Reginaa; Grootjans, Saskerc,d; Biavatti, Maique W.b; Vandenabeele, Peterc,d; D’Herde, KatharinaeAuthor Information aChemical and Pharmaceutical Research Group, Health Sciences Center, University of Vale do Itajai, Itajai bLaboratory for Farmacognosy, Departement of Farmaceutical Sciences, Health Sciences Center, Federal University of Santa Catarina, Florianópolis, Brazil cDepartment for Molecular Biomedical Research, VIB Departments of dBiomedical Molecular Biology eHuman Anatomy, Ghent University, Ghent, Belgium Correspondence to Katharina D’Herde, Department of Basic Medical Sciences, Ghent University, De Pintelaan 185 (B3, 4th floor), 9000 Ghent, Belgium Tel: +32 933 25244; fax: +32 933 23809; e-mail: [email protected] Received August 29, 2011 Accepted June 10, 2012 Anti-Cancer Drugs: October 2012 - Volume 23 - Issue 9 - p 883-896 doi: 10.1097/CAD.0b013e328356cad9 Buy Metrics Abstract 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. © 2012 Lippincott Williams & Wilkins, Inc.