Artemisia annua herbal preparations – Antitumor activity, analytical characterization, and identification of potential anticancer ingredients
Lang, Sophia J.
InstitutionsUKU. Institut für Naturheilkunde und Klinische Pharmakologie
UKU. Klinik für Frauenheilkunde und Geburtshilfe
In the past few years, the Chinese medicinal plant Artemisia annua L., and in particular semisynthetic derivatives of artemisinin, have gained increasing attention for their potential anticancer activity. However, only little is known about Artemisia annua extracts and numerous bioactive compounds therein, beside the better explored artemisinin. Therefore, chemical characterization of an Artemisia annua extract was conducted. The extract is devoid of detectable artemisinin but exhibits remarkable antiproliferative efficacies on highly metastatic triple negative human breast cancer (TNBC) MDA-MB-231 cells and other treatment-resistant cancer cells. The most abundant components of the Artemisia annua extract are 6,7-dimethoxy-coumarin, chrysosplenol D, casticin and arteannuic acid. The Artemisia annua extract inhibits the viability of breast (MDA-MB-231 and MCF-7), pancreas (MIA PaCa-2), prostate (PC-3) and non-small cell lung cancer (A549) cells, whereas the viability of normal mammary epithelial cells and peripheral blood mononuclear cells remains unaffected at equal concentrations. Similarly, the extract ingredients chrysosplenol D and casticin exhibit selective cytotoxicity to cancer cells, whereas 6,7-dimethoxycoumarin and arteannuic acid exhibit no toxicity to any other of the analyzed cancer cell lines. The Artemisia annua extract and the flavonols chrysosplenol D and casticin inhibit the cell cycle progression and induce apoptosis. To examine the in vivo antiproliferative efficacy of the extract, chrysosplenol D, and casticin, their effects on TNBC MDA-MB-231 xenografts grown on the chick chorioallantoic membrane (CAM) and in nude mice were analyzed. The Artemisia annua extract effectively inhibits tumor growth in nude mice and on the CAM. Likewise, chrysosplenol D and casticin inhibit the MDA-MB-231 proliferation in the CAM assay. Notably, no systemic toxicity on the chicken embryos could be observed after treatment with the Artemisia annua extract, chrysosplenol D, or casticin. The systemic administration of the Artemisia annua extract to nude mice reveals good tolerability. Chrysosplenol D induces ERK1/2 activation. Although ERK1/2 kinases are often activated in cancer promoting cell proliferation, under certain conditions upregulated ERK1/2 kinases can also mediate apoptosis. In contrast to casticin, the toxicity induced by chrysosplenol D in MDA-MB-231 cells is mediated by ERK1/2. To sum up, this work provides evidence for an antitumor activity of an Artemisia annua extract, that is marketed as a dietary supplement, against highly metastatic TNBC. Active extract ingredients have been identified and it is shown for the first time that the flavonol chrysosplenol D exhibits antitumor activity against TNBC and inhibits the proliferation of a variety of treatment-resistant cancer cells. This work might contribute to further successful investigations of Artemisia annua-derived compounds and their potential therapeutic use.
Subject HeadingsEinjähriger Beifuß [GND]
Artemisia annua [MeSH]
Breast neoplasms [MeSH]
Artemisinins; Therapeutic use [MeSH]
Flavonols; Therapeutic use [MeSH]