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Anticancer activities of sesquiterpene lactones from Cyathocline purpurea in vitro

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Abstract

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, 9β-acetoxycostunolide and 9β-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, 9β-acetoxycostunolide and 9β-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 μg/mL. In L1210 model, santamarine and 9β-acetoxycostunolide inhibited L1210 cell growth, colony formation and [3H]-thymidine incorporation in time- and concentration-dependent manners. Flow cytometry studies showed that santamarine and 9β-acetoxycostunolide blocked L1210 cells in the G2/M phase of the cell cycle. DAPI staining and caspase activity assays showed santamarine and 9β-acetoxycostunolide induced apoptosis and activated caspase 3 in L1210 cells.

Conclusions

These results indicated that santamarine, 9β-acetoxycostunolide and 9β-acetoxyparthenolide exhibit significant anticancer activities in vitro. The inhibitory effects of santamarine and 9β-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 9β-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 α-methylene-γ-lactone moiety present in santamarine, 9β-acetoxycostunolide and 9β-acetoxyparthenolide. It may also be related to suppression of microtubular proteins. Santamarine and 9β-acetoxycostunolide induced apoptosis of L1210 cells via activation of caspase 3.

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Author notes

  1. Guoyi Ma

    Present address: National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA

Authors and Affiliations

  1. Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia

    Guoyi Ma & Andrew H. T. Cheung

  2. Department of Cancer Medicine, The University of Sydney, Sydney, NSW, 2006, Australia

    Li Chong & Martin H. N. Tattersall

  3. The Experiment Center of Yunnan University, 650031, Kunming, China

    Zuqiang Li

Authors
  1. Guoyi Ma
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  2. Li Chong
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  3. Zuqiang Li
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  4. Andrew H. T. Cheung
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  5. Martin H. N. Tattersall
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Correspondence to Guoyi Ma.

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Ma, G., Chong, L., Li, Z. et al. Anticancer activities of sesquiterpene lactones from Cyathocline purpurea in vitro. Cancer Chemother Pharmacol 64, 143–152 (2009). https://doi.org/10.1007/s00280-008-0863-y

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  • DOI: https://doi.org/10.1007/s00280-008-0863-y

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