title: Cytotoxic and apoptosis-inducing activities of steviol and isosteviol derivatives against human cancer cell lines.
abstract: Seventeen steviol derivatives, i.e., 2-18, and 19 isosteviol derivatives, i.e., 19-37, were prepared from a diterpenoid glycoside, stevioside (1). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, nine steviol derivatives, i.e., 5-9 and 11-14, and five isosteviol derivatives, i.e., 28-32, exhibited activities with single-digit micromolar IC(50) values against one or more cell lines. All of these active compounds possess C(19)-O-acyl group, and among which, ent-kaur-16-ene-13,19-diol 19-O-4',4',4'-trifluorocrotonate (14) exhibited potent cytotoxicities against four cell lines with IC(50) values in the range of 1.2-4.1 μM. Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis. These results suggested that acylation of the 19-OH group of kaurane- and beyerane-type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis-inducing activity.
authors: College of Science and Technology, Nihon University, 1-8-14 Kanda Surugadai, Tokyo 101-8308, Japan. ukiya.motohiko@nihon-u.ac.jp
authors: Motohiko
authors: M
authors: Ukiya
authors: Shingo
authors: S
authors: Sawada
authors: Takashi
authors: T
authors: Kikuchi
authors: Yasunori
authors: Y
authors: Kushi
authors: Makoto
authors: M
authors: Fukatsu
authors: Toshihiro
authors: T
authors: Akihisa
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D036625:Stevia / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; C515747:isosteviol; C012042:steviol