Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular mechanisms.
Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants used in traditional medicine for the treatment of inflammatory diseases. In recent years, the anti-cancer property of various SLs has attracted a great deal of interest and extensive research work has been carried out to characterize the anti-cancer activity, the molecular mechanisms, and the potential chemopreventive and chemotherapeutic application of SLs. In this review, we attempt to summarize the current knowledge of the anti-cancer properties of SLs by focusing on the following important issues. First, we discuss the structure-activity relationship of SLs. All SLs contain a common functional structure, an alpha-methylene-gamma-lactone group, and this important chemical characteristic means that the thiol-reactivity of SLs is an underlying mechanism responsible for their bioactivities. Second, we assess the experimental evidence for the anti-cancer function of SLs obtained from both in vitro cell culture and in vivo animal models. Various SLs have been demonstrated to execute their anti-cancer capability via inhibition of inflammatory responses, prevention of metastasis and induction of apoptosis. Thirdly, we outline the molecular mechanisms involved in the anti-cancer activity of SLs, in particular, the SL-thiols reaction, the effect of SLs on cell signaling pathways such as nuclear transcription factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPK). Finally, we recapitulate some important SLs with regards to their anti-cancer activities and their potential in anti-cancer drug development. Taken together, many SLs are emerging as promising anti-cancer agents with potential applications in both cancer chemotherapy and chemoprevention.
Department of Community, Occupational and Family Medicine, Faculty of Medicine, National University of Singapore, Republic of Singapore.
Siyuan
S
Zhang
Yen-Kim
YK
Won
Choon-Nam
CN
Ong
Han-Ming
HM
Shen
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D012717:Sesquiterpenes