Anticancer activities of sesquiterpene lactones from Cyathocline purpurea in vitro

作者：Ma, Guoyi^*; Chong, Li; Li, Zuqiang; Cheung, Andrew H. T.; Tattersall, Martin H. N.

来源：Cancer Chemotherapy and Pharmacology, 2009, 64(1): 143-152.

DOI：10.1007/s00280-008-0863-y

• Sesquiterpene lactone
• Cell growth
• Cytotoxicity
• DNA synthesis
• Cell cycle
• Apoptosis
• Caspase

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, 9 beta-acetoxycostunolide and 9 beta-acetoxyparthenolide isolated from C. purpurea in vitro. @@@ 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(A (R)) 3/7 assay kit. @@@ Santamarine, 9 beta-acetoxycostunolide and 9 beta-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 IC50 in the range of 0.16-1.3 mu g/mL. In L1210 model, santamarine and 9 beta-acetoxycostunolide inhibited L1210 cell growth, colony formation and [H-3]-thymidine incorporation in time- and concentration-dependent manners. Flow cytometry studies showed that santamarine and 9 beta-acetoxycostunolide blocked L1210 cells in the G(2)/M phase of the cell cycle. DAPI staining and caspase activity assays showed santamarine and 9 beta-acetoxycostunolide induced apoptosis and activated caspase 3 in L1210 cells. @@@ These results indicated that santamarine, 9 beta-acetoxycostunolide and 9 beta-acetoxyparthenolide exhibit significant anticancer activities in vitro. The inhibitory effects of santamarine and 9 beta-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 9 beta-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, 9 beta-acetoxycostunolide and 9 beta-acetoxyparthenolide. It may also be related to suppression of microtubular proteins. Santamarine and 9 beta-acetoxycostunolide induced apoptosis of L1210 cells via activation of caspase 3.

• 出版日期2009-6
• 单位云南大学