Growth inhibition and induction of early apoptosis by arenicolsterol A, a novel cytotoxic enolic sulphated sterol from the marine annelid, Arenicola cristata

Abstract

Arenicolsterol A (ASA), a novel cytotoxic enolic sulphated sterol, was isolated from the marine annelid, Arenicola cristata (AC). Growth inhibition of this compound on cancer cell lines was determined by MTT assay and suppression of tumour stem cells colony formation. The results showed that ASA was selectively cytotoxic on HeLa cell line (IC₅₀ = 6.00 ± 1.16 μmol L^− 1 on HeLa cell line, IC₅₀ = 10.85 ± 0.97 μmol L^− 1 on 929 cell line and 14.72 ± 1.55 μmol L^− 1 on NCI-h6 cell line). In addition, the apoptosis induced by ASA was verified from monitoring the stainability with Annexin V and propidium iodine by a fluorescence-activated cell sorter. The experimental data confirmed that ASA could induce apoptosis in HeLa cells by arresting early stage in apoptosis. Meanwhile, the apoptosis was found to be correlative with the inhibition of the protein tyrosine phosphatases (cdc25A, cdc25B, JSP1, etc). Therefore, ASA might be a novel promising precursor of anticancer medicines.

Keywords:

• Natural product
• Arenicola cristata
• Arenicolsterol A
• Anticancer
• Apoptosis

Acknowledgements

This work was supported by NSFC (20525519), TRAPOYT and Shanghai SK R&D Foundation. Special thanks to the technical staff of the Marine Biology Research Centre, Naval Medical Institute, Shanghai, China.