title: Cytotoxic compounds from the stems of Cinnamomum tenuifolium.
abstract: Three new butanolides, tenuifolide A (1), isotenuifolide A (2), and tenuifolide B (3), a new secobutanolide, secotenuifolide A (4), and one new sesquiterpenoid, tenuifolin (5), along with 16 known compounds were isolated from the stems of Cinnamomum tenuifolium. Their structures were determined by spectroscopic analyses. Compound 4 was found to induce apoptotic-related DNA damage, increase sub-G1 cells, and inhibit the growth of human prostate cancer cells, DU145. In addition, treatment with 4 significantly increased intracellular H2O2 and/or peroxide. The results show that 4 induced (a) noticeable reduction of mitochondrial transmembrane potential (DeltaPsim); (b) significant increase in the ratio of cytochrome c concentration (cytosol/mitochondria); and (c) subsequent activation of caspase-9/caspase-3. Antiproliferation caused by 4 was found to markedly decrease when pretreated with caspase-9/caspase-3 inhibitor. In ROS scavenging, antioxidant, NADPH oxidase, and NO inhibitor studies, pretreatment of DU145 cells with either DPI, dexamethasone, L-NAME, or mannitol decreased 4-induced intracellular DCF fluorescence of ROS. These results suggest that an increase of H2O2 and/or peroxide by 4 is the initial apoptotic event and 4 has anticancer effects on DU145 cells.
authors.affiliation: Department of Parasitology and Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, Republic of China.
authors.forename: Rong-Jyh
authors.initials: RJ
authors.lastname: Lin
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Cheng
authors.forename: Jin-Cherng
authors.initials: JC
authors.lastname: Huang
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Lo
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Yeh
authors.forename: Chung-Min
authors.initials: CM
authors.lastname: Yen
authors.forename: Chin-Mei
authors.initials: CM
authors.lastname: Lu
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Chen
mesh_terms: D006801:Humans; D008297:Male; D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D061945:Caspase Inhibitors; D027424:Cinnamomum / Q000737:chemistry; D045304:Cytochromes c / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018547:Plant Stems / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D013624:Taiwan; D045786:Diterpenes, Kaurane
chemical_list: D015107:4-Butyrolactone; D000972:Antineoplastic Agents, Phytogenic; D061945:Caspase Inhibitors; D045304:Cytochromes c; D006861:Hydrogen Peroxide; C545044:secotenuifolide A; C545042:tenuifolide A; C545043:tenuifolide B; C532370:tenuifolin diterpene; D045786:Diterpenes, Kaurane