Hypoxia enhances cytotoxicity of wedelolactone to breast cancer cells

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Year of publication 2014
Type Conference abstract
Description Microenvironment of solid tumors is characterized by hypoxia as a result of malformed vasculature and inadequate perfusion. Tumor cells, however, developed various strategies to adapt to hypoxic microenvironment. Numerous studies reported link between severe hypoxia and cancer progression. Nevertheless, recent studies have shown that hypoxia can affect the effectiveness of chemotherapy as well. Wedelolactone is a plant polyphenolic coumestan with in vitro and in vivo anti-cancer properties. Many proteins and signaling pathways were identified as wedelolactone targets including NFkB, steroid receptors, MAPK kinases and topoisomerase II. We have demonstrated that induction of oxidative stress represent another mechanism of its cytotoxicity. This study was designed to analyze the modulatory effect of hypoxia to cytotoxicity of wedelolactone to MDA-MB-231 and T47D breast cancer cells. We observed that hypoxia significantly enhanced pro-apoptotic effect of wedelolactone in both cell lines as documented by analysis of nuclear morphology, PARP cleavage and phosphatidylserine externalization. The enhancing effect of hypoxia was associated with altered ROS kinetics and stress signaling response. We believe that cytotoxicity of newly developed/tested chemotherapeutics in conditions of specific tumor microenvironment has to be considered in their pre-clinical studies.
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