Santamarine

Anticancer activities of sesquiterpene lactones from Cyathocline purpurea in vitro.[Pubmed:18998133]

Cancer Chemother Pharmacol. 2009 Jun;64(1):143-52.

PURPOSE: Cyathocline purpurea has been traditionally used to treat various diseases including cancers for many years. However, these applications of C. purpurea have not been supported by pharmacological investigation. The objective of this study is to investigate the anticancer activities of three main constituents such as Santamarine, 9beta-acetoxycostunolide and 9beta-acetoxyparthenolide isolated from C. purpurea in vitro. METHODS: Cell viability was determined by trypan blue exclusion and methylene blue assays. Colony formation was assessed by microtitration cloning assay. DNA synthesis was determined by tritiated thymidine incorporation assay. Cell cycle analysis was carried out by flow cytometry. Apoptosis was observed by DAPI staining assay and Caspase 3/7 activities was measured using Caspase-Glo 3/7 assay kit. RESULTS: Santamarine, 9beta-acetoxycostunolide and 9beta-acetoxyparthenolide inhibited the growth of L1210 murine leukaemia, CCRF-CEM human leukaemia, KB human nasopharyngeal carcinoma, LS174T human colon adenocarcinoma and MCF 7 human breast adenocarcinoma cells in vitro, with IC(50) in the range of 0.16-1.3 microg/mL. In L1210 model, Santamarine and 9beta-acetoxycostunolide inhibited L1210 cell growth, colony formation and [(3)H]-thymidine incorporation in time- and concentration-dependent manners. Flow cytometry studies showed that Santamarine and 9beta-acetoxycostunolide blocked L1210 cells in the G(2)/M phase of the cell cycle. DAPI staining and caspase activity assays showed Santamarine and 9beta-acetoxycostunolide induced apoptosis and activated caspase 3 in L1210 cells. CONCLUSIONS: These results indicated that Santamarine, 9beta-acetoxycostunolide and 9beta-acetoxyparthenolide exhibit significant anticancer activities in vitro. The inhibitory effects of Santamarine and 9beta-acetoxycostunolide on L1210 cells are cytotoxic rather than just cytostatic. They block mitosis and reduce uptake of thymidine. The mechanism of the cytotoxicity of Santamarine and 9beta-acetoxycostunolide to L1210 cells could be related to alkylation of the sulfhydryl enzymes involved in nucleic acids and protein synthesis, as previously found for other sesquiterpenes with the alpha-methylene-gamma-lactone moiety present in Santamarine, 9beta-acetoxycostunolide and 9beta-acetoxyparthenolide. It may also be related to suppression of microtubular proteins. Santamarine and 9beta-acetoxycostunolide induced apoptosis of L1210 cells via activation of caspase 3.

Isolation and characterization of the sesquiterpene lactones costunolide, parthenolide, costunolide diepoxide, santamarine, and reynosin from Magnolia grandiflora L.[Pubmed:641720]

J Pharm Sci. 1978 Mar;67(3):347-50.

The germacranolide sesquiterpene lactones costunolide, parthenolide, and costunolide diepoxide were isolated from the leaves of Magnolia grandiflora L. Costunolide diepoxide might be, at least in part, an artifact derived from air oxidation of parthenolide. The root bark yielded only costunolide together with the two eudesmanolides, Santamarine and reynosin. In an attempt to synthesize costunolide diepoxide, the action of m-chloroperbenzoic acid on parthenolide and on costunolide was studied. The products were costunolide diepoxide from parthenolide and the two cyclized derivatives, Santamarine and reynosin, from costunolide. The elusive 1,10-epoxide was obtained by epoxidizing costunolide using a biphasic system containing sodium bicarbonate. Under these conditions, epoxidation of costunolide took place without cyclization.