Montag, 29. August 2011

Antitumor Activity of Artemisinin and Its Derivatives

Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 247597, 18 pages

Review Article
Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

Maria P. Crespo-Ortiz1 and Ming Q. Wei2

1 Department of Biomedical Science, Faculty of Basic and Health Science, Santiago de Cali University, Pampalinda Campus, Cali, Colombia
2 Division of Molecular and Gene Therapies, Griffith Health Institute and School of Medical Science, Griffith University, Gold Coast Campus, Southport, QLD 4222, Australia


Improvement of quality of life and survival of cancer patients will be greatly enhanced by the development of highly effective drugs to selectively kill malignant cells. Artemisinin and its analogs are naturally occurring antimalarials which have shown potent anticancer activity. In primary cancer cultures and cell lines, their antitumor actions were by inhibiting cancer proliferation, metastasis, and angiogenesis. In xenograft models, exposure to artemisinins substantially reduces tumor volume and progression. However, the rationale for the use of artemisinins in anticancer therapy must be addressed by a greater understanding of the underlying mechanisms involved in their cytotoxic effects. The primary targets for artemisinin and the chemical base for its preferential effects on heterologous tumor cells need yet to be elucidated. The aim of this paper is to provide an overview of the recent advances and new development of this class of drugs as potential anticancer agents.

Antiproliferative effects of artemisinin on human breast can... : Anti-Cancer Drugs

Anticancer Drugs. 2012 Apr;23(4):370-9. doi: 10.1097/CAD.0b013e32834f6ea8.

Antiproliferative effects of artemisinin on human breast cancer cells requires the downregulated expression of the E2F1 transcription factor and loss of E2F1-target cell cycle genes.

Artemisinin, a sesquiterpene phytolactone derived from Artemisia annua, is a potent antimalarial compound with promising anticancer properties, although the mechanism of its anticancer signaling is not well understood. Artemisinin inhibited proliferation and induced a strong G1 cell cycle arrest of cultured MCF7 cells, an estrogen-responsive human breast cancer cell line that represents an early-stage cancer phenotype, and effectively inhibited the in-vivo growth of MCF7 cell-derived tumors from xenografts in athymic nude mice. Artemisinin also induced a growth arrest of tumorigenic human breast cancer cell lines with preneoplastic and late stage cancer phenotypes, but failed to arrest the growth of a nontumorigenic human mammary cell line. Concurrent with the cell cycle arrest of MCF7 cells, artemisinin selectively downregulated the transcript and protein levels of the CDK2 and CDK4 cyclin-dependent kinases, cyclin E, cyclin D1, and the E2F1 transcription factor. Analysis of CDK2 promoter-luciferase reporter constructs showed that the artemisinin ablation of CDK2 gene expression was accounted for by the loss of CDK2 promoter activity. Chromatin immunoprecipitation revealed that artemisinin inhibited E2F1 interactions with the endogenous MCF7 cell CDK2 and cyclin E promoters. Moreover, constitutive expression of exogenous E2F1 prevented the artemisinin-induced cell cycle arrest and downregulation of CDK2 and cyclin E gene expression. Taken together, our results demonstrate that the artemisinin disruption of E2F1 transcription factor expression mediates the cell cycle arrest of human breast cancer cells and represents a critical transcriptional pathway by which artemisinin controls human reproductive cancer cell growth.