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ABSTRACT: Ursolic acid (UA) is a pentacyclic triterpenoid with promising cancer chemopreventive properties. A better understanding of the mechanisms underlying anticancer activity of UA is needed for further development as a clinically useful chemopreventive agent. Here, we found that both endoplasmic reticulum (ER) stress and autophagy were induced by UA in MCF-7 human breast cancer cells. Surprisingly, ER stress was identified as an effect rather than a cause of UA-induced autophagy. Autophagy-dependent ER stress protected the cells from UA-induced apoptosis through EIF2AK3-mediated upregulation of MCL1. Activation of MAPK1/3 but not inhibition of MTOR pathway contributed to UA-induced cytoprotective autophagy in MCF-7 cells. Our findings uncovered a novel cellular mechanism involved in the anticancer activity of UA, and also provided a useful model to study biological significance and mechanisms of autophagy-mediated ER stress.
Autophagy 11/2012; 9(2). · 7.45 Impact Factor
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ABSTRACT: Previous studies have shown that Pseudolaric acid B (PAB), a medicinal plant-derived terpenoid, is a promising chemopreventive or therapeutic agent against various types of cancer. However, less is known regarding its activity against prostate cancer. The objective of the current study is designed to determine the anti-prostate cancer effects of PAB. We demonstrated here that PAB was highly effective against both androgen-dependent (LNCaP) and androgen-independent prostate cancer cells (PC-3 and DU145) through the mechanisms involved in induction of G2/M cell cycle arrest, caspase-dependent apoptosis and autophagic cell death. Furthermore, PAB can greatly sensitize these two aggressive androgen-independent prostate cancer cells to ABT-737-induced cytotoxicity. Our findings suggest that PAB holds excellent potential as either novel chemopreventive agent or enhancer of therapeutic drug against prostate cancer. Copyright © 2012 John Wiley & Sons, Ltd.
Phytotherapy Research 08/2012; · 2.09 Impact Factor
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ABSTRACT: Curcumin and methylseleninic acid (MSeA) are well-documented dietary chemopreventive agents. Apoptosis appears to be a major mechanism for both agents to exert anti-cancer activity. The purpose of the present study was designed to determine whether the apoptotic effect on human cancer cells can be enhanced by combining curcumin with MSeA. Apoptosis was evaluated by Annexin V staining of externalized phosphatidylserine by flow cytometry. Expression of protein was analyzed by Western blotting. Localization of apoptosis-inducing factor (AIF) was detected by immunocytochemistry. RNA interference was employed to inhibit expression of specific protein. We found here that combining curcumin with MSeA led to a significantly enhanced apoptosis in both MDA-MB-231 breast cancer cells and DU145 prostate cancer cells. Further mechanistic investigations revealed that curcumin treatment alone caused a concentration dependent upregulation of Mcl-1, which can be overcome by combining it with MSeA. In line with the Mcl-1 reduction, an enhanced mitochondrial permeability transition and AIF nuclear translocation by the combination were achieved. In addition, an increased suppression of focal adhesion kinase activity was observed in the combination-treated cells which were associated with cell detachment-induced apoptosis by the combination. Our findings suggest that curcumin/MSeA combination holds excellent potential for improving their efficacy against human breast and prostate cancer through enhanced apoptosis induction. © 2012 Wiley Periodicals, Inc.
Molecular Carcinogenesis 06/2012; · 3.16 Impact Factor
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Operations Research. 01/2005; 53:501-515.
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ABSTRACT: In most large cities, the taxi industry is subject to various types of regulation, such as entry restrictions and price controls, and economists have examined the economic consequences of such regulation extensively. Unfortunately, in conventional economic analyses of competition and regulation in the taxi industry little attention has been paid to one important issue: congestion externalities due to both occupied and vacant taxi movements together with normal vehicular traffic. This study investigates the nature of equilibrium and regulation in the taxi market by taking account of congestion externalities and adopting a realistic distance-based and delay-based taxi fare structure. The monopoly, the social optimum and the stable competitive solutions are examined and illustrated with a numerical example.
Transportation Research Part A: Policy and Practice.
