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, 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.remarkable result. The study of its anti – malarial properties probes into another promising anti – cancer property of Sweet wormwood Artemisinins.
More anti-cancer research and clincal trials with Artemisnin can be read in this article
Artemisinins anti cancer mechanism is currently being intensively researched; several evidences have aid the formulation of a model in which Sweet Wormwood extract Artemisinins kills cancer cells by inducing irreversible damage through ROS (reactive oxygen species) targeting cancer cells with high iron content. It also induces apoptosis in cancer cells forcing the mutated cells to commit programmed suicide. The Developmental Therapeutics Program of the National Cancer Institute, USA, analyzes the effect of Artemisinins on 55 human cancer lines, and proved the anti-cancer activity against several types of cancers including leukemia, colon cancer cell lines, melanoma, breast, ovarian, prostate, central nervous system, and renal cancer cell lines. Previous studies also shed light into its anti – angiogenesis property, effecting a cellular stasis, thus preventing proliferation and metastasis of cancer cells.
In the light of breast cancer, researchers have also proven in early studies that Artemisinins demonstrate actions on breast cancer. In a study reported in 2008 by Sundar et al, treatment of MCF7 cells (estrogen responsive human breast cancer cell line that expresses both estrogen receptor-alpha (ERα) and estrogen receptor-beta (ERβ)) with Artemisinins, phytochemical from Sweet Wormwood, effectively blocked estrogen stimulated cell cycle progression. Artemisinins is proven to down regulate ERα protein and its transcription with few to no regulatory action on ERβ, reversing the high ERα : ERβ ratio to a level near physiologic level.
Earlier study by Lai and Singh in 2006, designed in rats suggests the potential Artemisinins activity in breast cancer cells. Rats exposed to potent mammary carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA), are orally administered Artemisinins. The results reflect inhibition of the mammary cancers occurrence. Since these cancer cells are estrogen sensitive, the result therefore is extrapolated to a probable mechanism by which Artemisinins disrupt estrogenic promotion in the rat mammary epithelial probably by interfering through the ERα activity.
Translating the study in human cancer cells, Sundar et al revealed that Artemisinins down regulates ERα promoter thus reducing its transcription, keeping its level low. Artemisinins treatment also ablates the induction of endogenous progesterone receptors transcripts by either E2 or PPT, and inhibited the estrogenic stimulation of a luciferase reporter plasmid driven by consensus estrogen response elements (ERE). Chromatin Immunoprecipitation assays demonstrated that Artemisinins extensively down regulates the level of ERα bound to progesterone receptor promoter, whereas the level of bound ERβ remains unchanged. The results translate into low proliferation state after the treatment with Artemisinins, a state seen normally in human mammary epithelial cells.
With these results, there is a strong suggestion for Artemisinins as adjuvant therapy together with the current anti – estrogen therapy. The combination suggests positive synergism with promising significant lower side effects of anti – estrogen therapy. Recalling the long term treatment of anti – estrogen in patient with estrogen sensitive breast cancer, the combination with naturally occurring phytochemical from Sweet wormwood, Artemisinins will benefit patients from lowering the systemic exposure of anti – estrogens side effects.
