Molecular target of an anti-cancer compound from leaves of Clausena harmandiana (Pierre)

Abstract

Clausena harmandiana (Pierre) Guillaumin or Song faa dong (in Thai), is classified in Family Rutaceae. Previous study, a coumarin compound designated CHA-01 was isolated from leave extract of C. harmandiana with inhibitory activity against calcium signaling in a ZDS1 null mutant yeast Saccharomyces cerevisiae (delta zds1). However, not much has been known on biological activity of this coumarin. In the past, some other coumarins were reported to contain anti-cancer activity. The aim of this research was to study molecular mechanism on antiproliferation activity of CHA-01 in Jurkat T cells. The results revealed that CHA-01 showed anti-proliferative activity in several cell lines including Jurkat (Lymphocytic leukemic cell line), KATO III (Stomach cancer cell line) and THP1 (Monocytic leukemic cell line) by MTT assay. Jurkat T cell line was the most sensitity cell line to CHA-01 treatment with IC50 value of 0.67 μM. It contained no cytotoxic activity against normal lymphocytes up to 10 μM. Flow cytometric analysis revealed that the CHA-01 caused cell cycle arrest at S phase in Jurkat T cells as a result from inhibition of DNA synthesis. Moreover, CHA-01 induced apoptotic cell death in the Jurkat T cells. Our results revealed the role(s) of CHA-01 on its anti-cancer activity especially against lymphocytic leukemia. Future study will utilize proteomic analysis on expression level of proteins in CHA-01 treated Jurkat T cells.