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Yu HY, Kim SO, Jin CY, et al. β-lapachone-Induced Apoptosis of Human Gastric Carcinoma AGS Cells Is Caspase-Dependent and Regulated by the PI3K/Akt Pathway. Biomol Ther (Seoul). 2014;22(3):184-92doi: 10.4062/biomolther.2014.026.
Yu, H. Y., Kim, S. O., Jin, C. Y., Kim, G. Y., Kim, W. J., Yoo, Y. H., & Choi, Y. H. (2014). β-lapachone-Induced Apoptosis of Human Gastric Carcinoma AGS Cells Is Caspase-Dependent and Regulated by the PI3K/Akt Pathway. Biomolecules & therapeutics, 22(3), 184-92. https://doi.org/10.4062/biomolther.2014.026
Yu, Hai Yang, et al. "β-lapachone-Induced Apoptosis of Human Gastric Carcinoma AGS Cells Is Caspase-Dependent and Regulated by the PI3K/Akt Pathway." Biomolecules & therapeutics vol. 22,3 (2014): 184-92. doi: https://doi.org/10.4062/biomolther.2014.026
Yu HY, Kim SO, Jin CY, Kim GY, Kim WJ, Yoo YH, Choi YH. β-lapachone-Induced Apoptosis of Human Gastric Carcinoma AGS Cells Is Caspase-Dependent and Regulated by the PI3K/Akt Pathway. Biomol Ther (Seoul). 2014 May;22(3):184-92. doi: 10.4062/biomolther.2014.026. PMID: 25009698; PMCID: PMC4060078.
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Biomol Ther (Seoul). 2014 May;22(3):184-92. doi: 10.4062/biomolther.2014.026.

β-lapachone-Induced Apoptosis of Human Gastric Carcinoma AGS Cells Is Caspase-Dependent and Regulated by the PI3K/Akt Pathway.

Biomolecules & therapeutics

Hai Yang Yu, Sung Ok Kim, Cheng-Yun Jin, Gi-Young Kim, Wun-Jae Kim, Young Hyun Yoo, Yung Hyun Choi

Affiliations

  1. College of Natural Resources and Life Science, Dong-A University, Busan 604-714.
  2. Team for Scientification of Korean Medical Intervention (BK21 Plus) & Department of Herbal Pharmacology, College of Oriental Medicine, Daegu Haany University, Daegu 706-828.
  3. School of Pharmaceutical Science, Zhengzhou University, Henan 450001, China.
  4. Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756.
  5. Department of Urology, Chungbuk National University College of Medicine, Cheongju 361-804.
  6. Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan 602-714.
  7. Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052 ; Anti-Aging Research Center & Blue-Bio Industry RIC, Dongeui University, Busan 614-714, Republic of Korea.

PMID: 25009698 PMCID: PMC4060078 DOI: 10.4062/biomolther.2014.026

Abstract

β-lapachone is a naturally occurring quinone that selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further elaborated. In this study, we investigated the effects of β-lapachone on the induction of apoptosis in human gastric carcinoma AGS cells. β-lapachone significantly inhibited cellular proliferation, and some typical apoptotic characteristics such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells were observed in β-lapachone-treated AGS cells. Treatment with β-lapachone caused mitochondrial transmembrane potential dissipation, stimulated the mitochondria-mediated intrinsic apoptotic pathway, as indicated by caspase-9 activation, cytochrome c release, Bcl-2 downregulation and Bax upregulation, as well as death receptor-mediated extrinsic apoptotic pathway, as indicated by activation of caspase-8 and truncation of Bid. This process was accompanied by activation of caspase-3 and concomitant with cleavage of poly(ADP-ribose) polymerase. The general caspase inhibitor, z-VAD-fmk, significantly abolished β-lapachone-induced cell death and inhibited growth. Further analysis demonstrated that the induction of apoptosis by β-lapachone was accompanied by inactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. The PI3K inhibitor LY29004 significantly increased β-lapachone-induced apoptosis and growth inhibition. Taken together, these findings indicate that the apoptotic activity of β-lapachone is probably regulated by a caspase-dependent cascade through activation of both intrinsic and extrinsic signaling pathways, and that inhibition of the PI3K/Akt signaling may contribute to β-lapachone-mediated AGS cell growth inhibition and apoptosis induction.

Keywords: Apoptosis; Caspase; PI3K/Akt; β-lapachone

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