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The Cytotoxic Effects Of Novel Persin Analogues on a Breast Cancer Cell LineRoberts et al. (2007) and Butt et al. (2006) previously found that persin, a compound isolated from avocado leaves, can induce apoptosis, or programmed cell death, in mammary epithelial cells of lactating mice in vivo and in certain human breast cancer cell lines in vitro. It has also been found that at higher doses, persin is cardiotoxic in mice and causes necrosis in mammary glands of lactating mammals (Oelrichs, 1995). Therefore, compounds with reduced mammary gland necrosis and cardiotoxicity but with the apoptotic effects of persin on breast cancer cells could be potential chemotherapeutic agents. Six novel analogues of persin have been synthesized to test their effects on MCF-7 breast cancer cells and MCF-10A normal breast epithelial cells. Cells cultured from each cell line were treated with each analogue at varying concentrations to determine potential cytotoxic doses. Cytotoxicity of the compounds was determined by a commercially available Cell Proliferation Assay. Compounds that were significantly cytotoxic were tested for apoptotic activity using an enzyme-linked immunosorbent assay. Three compounds were found to be cytotoxic to both cell lines, whereas the others had little to no impact on cell viability.
Epidermal Growth Factor Mediates Di-N-Octyl Phthalate-Induced Hepatocyte ProliferationCertain chemicals used in manufacturing plastics are linked to severe, negative health effects such as cancer. Di-N-Octylphthalate (DNOP) is a phthalate found in many plastics and has been linked with hepatocellular carcinoma. The aim of this research project was to study the effect of DNOP on both proliferation and differentiation of normal mouse hepatocytes. The expression of several growth factors and their receptors (epidermal growth factor (egf), epidermal growth factor receptor (egfr), insulin-like growth factor 1 (igf1), insulin-like growth factor 2 (igf2), insulin-like growth factor 1 receptor (igf1r), hepatocyte growth factor (hgf), and transforming growth factor-β (tgf-β )) was assessed in the normal hepatocyte AML-12 cell line by RT-PCR and qPCR. The rate of cell proliferation of AML-12 cells was measured using an MTT cell proliferation assay kit. Changes in cytoskeletal reorganization were assessed by immunostaining filamentous-actin using phalloidin staining. We found that DNOP at 0.1% caused an increase in expression of egf at 48h and tgf-β at 72h. This result was confirmed by Western blot. DNOP did not cause changes in any of the other studied genes. The rate of cell proliferation increased in those cells treated with 0.1% DNOP at 24, 48, and 72h. DNOP induced reorganization of the filamentous actin from basolateral to perinuclear. Our observation suggests that DNOP, through an increase in the expression of egf, acts as a proliferative agent in normal mouse hepatocytes, and through the expression of tgf-β, induces a reorganization of the filamentous-actin. These observations could be a mechanism by which DNOP leads to the development of hepatocellular carcinoma.