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Inhibition of PI3K/AKT Signaling Pathway Enhances Cordycepin-Induced Apoptosis in Human Gastric Cancer Cells
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 Title & Authors
Inhibition of PI3K/AKT Signaling Pathway Enhances Cordycepin-Induced Apoptosis in Human Gastric Cancer Cells
Lee, Hye Hyeon; Jeong, Jin-Woo; Choi, Yung Hyun;
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The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays a crucial role in cancer occurrence by promoting cell proliferation and inhibiting apoptosis. In the present study, we evaluated the effect of a PI3K inhibitor, LY294002, on the chemosensitivity of gastric cancer cells to cordycepin, a predominant functional component of the fungus Cordyceps militaris, in AGS human gastric cancer cells and investigated possible underlying cellular mechanisms. Our results revealed that cordycepin inhibited viability of AGS cells in a concentration-dependent manner and induced apoptosis, as determined by apoptotic cell morphologies and fluorescence-activated cell sorting analysis associated with attenuated activation of the PI3K/Akt signaling pathway. Treatment with cordycepin in combination with a subtoxic concentration of LY294002 enhanced cordycepin-induced cytotoxicity and apoptotic potentials in AGS cells. Sensitization of LY294002 to cordycepin-induced apoptosis was accompanied by activation of caspases (caspases-3, -8, and -9) and was concomitant with poly(ADP-ribose) polymerase cleavage. Moreover, LY294002 up-regulated pro-apoptotic Bax and enhanced truncation of Bid in cordycepin-treated AGS cells, which was connected with increased loss of mitochondrial membrane potential and release of cytochrome c from mitochondria to the cytosol. Taken together, these results indicate that inhibition of the PI3K/Akt signaling pathway could augment cordycepin-induced apoptosis in human gastric cancer cells by up-regulating caspase activity through mitochondrial dysfunction.
cordycepin;PI3K/Akt;AGS cells;apoptosis;caspase;
 Cited by
HepG2 간암세포에서 미토콘드리아 경로를 통한 개똥쑥 추출물의 Apoptosis 유도 효과,김보민;김근태;김은지;임은경;김상용;김영민;

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