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Wedelolactone affects breast cancer cells in biphasic manner

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NEHYBOVÁ Tereza BENEŠ Petr ŠMARDA Jan

Rok publikování 2014
Druh Konferenční abstrakty
Citace
Popis Natural polyphenols are a diverse group of compounds derived from various plants, such as soybean, tofu, vegetables, fruits, leaves or grains. Polyphenols have been found to have wide range of biological activities by acting as antioxidants and phytoestrogens. Moreover, polyphenols affect multiple signalling pathways related to carcinogenesis, tumor cell proliferation, inflammation, metastatic spread, angiogenesis, and drug resistance. Wedelolactone (WEL) is naturally occurring coumestan from Eclipta alba and Wedelia calendulacea. Recent studies highlighted the antitumour effects of WEL. WEL was found to suppress cell growth and to induce apoptosis of several types of cancer cells, an activity that was attributed to inhibition of DNA topoisomerase II?, suppression of DNA synthesis, inhibition of the NF?B and androgen receptors activities. This study was carried out in order to further define cancer-related activities of wedelolactone. We demonstrated a biphasic effect of wedelolactone on breast cancer cell lines. At nM concentrations, wedelolactone exerted a growth-stimulatory activity in estrogen receptor-positive cell lines MCF-7 and T47D along with activation of nuclear estrogen receptors (ER) and membrane ER-mediated signalling. The growth-stimulatory activity was not observed in the ER-negative MDA-MB-231 cell line. Nevertheless, the growth-inhibitory activity of wedelolactone at µM concentrations was ER-independent and associated with deregulation of p53, ERK and JNK signalling. In conclusion, we demonstrated that effects of wedelolactone on breast cancer cell growth, survival and cell signalling pathways are strongly dependent on concentration of this agent.
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