title: Cardiac glycosides from the seeds of Thevetia peruviana and their pro-apoptotic activity toward cancer cells.
abstract: Phytochemical investigation of the seeds of Thevetia peruviana resulted in the isolation of seven cardiac glycosides (1-7), including two new compounds (1 and 2). Cytotoxicity of them toward cancer cell lines P15 (human lung cancer cell), MGC-803 (human gastric cancer cells), SW1990 (human pancreatic cancer cells), and normal hepatocyte cell LO2 suggested that compound 1 could selectively inhibit the proliferation of cancer cell lines with IC50 from 0.05 to 0.15 μM. Pro-apoptotic activity revealed that it induced the apoptosis of MGC-803 cancer cells in a dose-dependent manner. Meanwhile, treatment of MGC-803 cancer cells with 1 resulted in diminution of pro-caspases 3 and 9 and activation of caspases 3 and 9, while it increased the Bax/Bcl-2 ratio in a dose-dependent manner. These meant that 1 induced the apoptosis of cancer cells by involving the intrinsic apoptotic pathway. In addition, the cell cycle distribution of MGC-803 cancer cells treated by 1 revealed that it could lead to cell cycle arrest at the G2/M phase. Altogether, this study suggested that compound 1 may exhibit anticancer activity by its capability of induction of intrinsic apoptosis and cell cycle arrest at G2/M phase.
authors.affiliation: a Department of Anatomy , Medical College, Jinan University , Guangzhou 510632 , China.
authors.forename: Huo-Yun
authors.initials: HY
authors.lastname: Cheng
authors.affiliation: b College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University , Shenyang 110016 , China.
authors.forename: Dan-Mei
authors.initials: DM
authors.lastname: Tian
authors.affiliation: c Institute of Traditional Chinese Medicine & Natural Products , College of Pharmacy, Jinan University , Guangzhou 510632 , China.
authors.forename: Jin-Shan
authors.initials: JS
authors.lastname: Tang
authors.affiliation: a Department of Anatomy , Medical College, Jinan University , Guangzhou 510632 , China.
authors.forename: Wei-Zai
authors.initials: WZ
authors.lastname: Shen
authors.affiliation: b College of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University , Shenyang 110016 , China.|c Institute of Traditional Chinese Medicine & Natural Products , College of Pharmacy, Jinan University , Guangzhou 510632 , China.
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Yao
mesh_terms: D002301:Cardiac Glycosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D012639:Seeds / Q000737:chemistry*; D031052:Thevetia / Q000737:chemistry*
chemical_list: D002301:Cardiac Glycosides; D004365:Drugs, Chinese Herbal; D053148:Caspase 3; D020169:Caspases
keywords: Apocynanceae; Thevetia peruviana; cardiac glycosides; cell cycle arrest; cytotoxicity; pro-apoptotic activity