Selective Cytotoxicity of Ponciri Fructus against Glucose-Deprived PANC-1 Human Pancreatic Cancer Cells via Blocking Activation of GRP78

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概要

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• Pancreatic cancer cells are sometimes exposed to stressful microenvironments such as glucose deprivation, hypoxia, and starvation of other nutrients. These stresses, which are characteristic of poorly vascularized solid tumors, activate the unfolded protein response (UPR). The UPR is a stress-signaling pathway present in tumor cells that is associated with molecular chaperone GRP78. Induction of GRP78 has been found to increase cell survival and decrease apoptotic potential through genetic alterations. Thus GRP78 may represent a novel target in the development of anticancer drugs. Here we established a novel screening program to identify chaperone modulators that exhibit preferential cytotoxic activity in glucose-deprived pancreatic cancer cells. During the course of our screening, we isolated an active substance, Ponciri Fructus (PF), from an herbal medicine source and identified it as a down-regulator of GRP78. As expected, PF inhibited expression of the GRP78 protein under glucose-deprivation conditions in a dose-dependent manner. Furthermore, it induced selective cytotoxicity against glucose-deprived cancer cells; this effect was not observed under normal growth conditions. We also detected apoptotic bodies on Hoechst staining and attempted to determine whether PF-induced apoptosis involved caspase-3 activation. Our results suggest that the GRP78-inhibitory action of PF was dependent on strict hypoglycemic conditions and that it resulted in the selective death of glucose-deprived pancreatic cancer cells.

• 社団法人 日本農芸化学会の論文

著者

• PARK Hae-Ryong

  Department of Food Science and Biotechnology, Kyungnam University 449 Wolyoung-dong

• CHA Mi-Ran

  Department of Food Science and Biotechnology, Kyungnam University

• YOON Mi-young

  Department of Food Science and Biotechnology, Kyungnam University

• SON Eun-Soon

  Department of Food Science and Biotechnology, Kyungnam University

• Son Eun-soon

  Department Of Food Science And Biotechnology Kyungnam University

関連論文

• Preventing the unfolded protein response via aberrant activation of 4E-binding protein 1 by versipelostatin
• Selective Cytotoxicity of Ponciri Fructus against Glucose-Deprived PANC-1 Human Pancreatic Cancer Cells via Blocking Activation of GRP78
• Selective Cytotoxicity of Ponciri Fructus against Glucose-Deprived PANC-1 Human Pancreatic Cancer Cells via Blocking Activation of GRP78
• Protective Effects of Paeonia lactiflora Pall on Hydrogen Peroxide-Induced Apoptosis in PC12 Cells

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