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Sagantang-induced Apoptotic Cell Death is Associated with the Activation of Caspases in AGS Human Gastric Carcinoma Cells
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  • Journal title : Journal of Life Science
  • Volume 25, Issue 12,  2015, pp.1384-1392
  • Publisher : Korean Society of Life Science
  • DOI : 10.5352/JLS.2015.25.12.1384
 Title & Authors
Sagantang-induced Apoptotic Cell Death is Associated with the Activation of Caspases in AGS Human Gastric Carcinoma Cells
Park, Cheol; Hong, Su Hyun; Choi, Sung Hyun; Lee, Se-Ra; Leem, Sun-Hee; Choi, Yung Hyun;
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Sagantang (SGT), a Korean multiherb formula comprising six medicinal herbs, Paeonia lactiflora Pall., Belamcanda chinensis (L.) DC, Gardenia jasminoides Ellis, Poria cocos Wolf, Cimicifuga heracleifolia Komarov, and Artractylodes japonica Koidzumi, was recorded in “Dongeuibogam.” The present study investigated the anticancer potential of SGT in AGS human gastric carcinoma cells. The results indicated that SGT treatment significantly inhibited the growth and viability of AGS cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, in addition to chromatin condensation and DNA fragmentation, and the accumulation of annexin-V positive cells. The induction of apoptotic cell death by the SGT treatment was associated with up-regulation of Fas protein expression, truncation of Bid, and down-regulation of the anti-apoptotic Bcl-2 protein. The SGT treatment also effectively induced the loss of mitochondrial membrane potential, which was associated with the activation of caspases (caspase-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase. However, a pan-caspase inhibitor significantly blocked the SGT-induced apoptosis and growth suppression in AGS cells. This study suggests that SGT induces caspase-dependent apoptosis through an extrinsic pathway by upregulating Fas, as well as through an intrinsic pathway by modulating Bcl-2 family members in AGS cells. The results suggest that SGT may be a potential chemotherapeutic agent for the control of human gastric cancer cells. However, further studies will be needed to confirm the potential of SGT in cancer prevention and therapy in an in vivo model and to identify biological active compounds of SGT.
AGS cells;apoptosis;caspase;mitochondrial membrane potential;Sagantang;
 Cited by
Asakura, T. and Ohkawa, K. 2004. Chemotherapeutic agents that induce mitochondrial apoptosis. Curr. Cancer Drug Targets 4, 577-590. crossref(new window)

Duriez, P. J. and Shah, G. M. 1997. Cleavage of poly (ADP-ribose) polymerase: a sensitive parameter to study cell death. Biochem. Cell Biol. 75, 337-349. crossref(new window)

Eastman, A. 1995. Assays for DNA fragmentation, endonucleases, and intracellular pH and Ca2+ associated with apoptosis. Methods Cell Biol. 46, 41-55. crossref(new window)

Fennell, D. A. and Chacko, A. 2008. Exploiting BH3 only protein function for effective cancer therapy. Front Biosci. 13, 6682-6692.

Fiandalo, M. V. and Kyprianou, N. 2012. Caspase control: protagonists of cancer cell apoptosis. Exp. Oncol. 34, 165-175.

Fulda, S. and Debatin, K. M. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25, 4798-4811. crossref(new window)

Hassan, M., Watari, H., AbuAlmaaty, A., Ohba, Y. and Sakuragi, N. 2014. Apoptosis and molecular targeting therapy in cancer. Biomed. Res. Int. 2014, 150845.

Hensley, P., Mishra, M. and Kyprianou, N. 2013. Targeting caspases in cancer therapeutics. Biol. Chem. 394, 831-843.

Hong, M. H., Kim, J. H., Bae, H., Lee, N. Y., Shin, Y. C., Kim, S. H. and Ko, S. G. 2010. Atractylodes japonica Koidzumi inhibits the production of proinflammatory cytokines through inhibition of the NF-kappaB/IkappaB signal pathway in HMC-1 human mast cells. Arch. Pharm. Res. 33, 843-851. crossref(new window)

Jourdain, A. and Martinou, J. C. 2009. Mitochondrial outer-membrane permeabilization and remodelling in apoptosis. Int. J. Biochem. Cell Biol. 41, 1884-1889. crossref(new window)

Kadenbach, B., Arnold, S., Lee, I. and Hüttemann, M. 2004. The possible role of cytochrome c oxidase in stress-induced apoptosis and degenerative diseases. Biochim. Biophys. Acta. 1655, 400-4008. crossref(new window)

Kasibhatla, S. and Tseng, B. 2003. Why target apoptosis in cancer treatment. Mol. Cancer Ther. 2, 573-580.

Kumar, H., Song, S. Y., More, S. V., Kang, S. M., Kim, B. W., Kim, I. S. and Choi, D. K. 2013. Traditional Korean east asian medicines and herbal formulations for cognitive impairment. Molecules 18, 14670-14693. crossref(new window)

Kyprianou, N., English, H. F. and Isaacs, J. T. 1998. Activation of a Ca2+-Mg2+-dependent endonuclease as an early event in castration-induced prostatic cell death. Prostate 13, 103-117.

Lavrik, I. N. 2010. Systems biology of apoptosis signaling networks. Curr. Opin. Biotechnol. 21, 551-555. crossref(new window)

Lee, J. H., Lee, D. U. and Jeong, C. S. 2009. Gardenia jasminoides Ellis ethanol extract and its constituents reduce the risks of gastritis and reverse gastric lesions in rats. Food Chem. Toxicol. 47, 1127-1131. crossref(new window)

Ola, M. S., Nawaz, M. and Ahsan, H. 2011. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol. Cell. Biochem. 351, 41-58. crossref(new window)

Ou, T. T., Wu, C. H., Hsu, J. D., Chyau, C. C., Lee, H. J., and Wang, C. J. 2011. Paeonia lactiflora Pall inhibits bladder cancer growth involving phosphorylation of Chk2 in vitro and in vivo. J. Ethnopharmacol. 135, 162-172. crossref(new window)

Park, H. and Kim, H. S. 2014. Korean traditional natural herbs and plants as immune enhancing, antidiabetic, chemopreventive, and antioxidative agents: a narrative review and perspective. J. Med. Food 17, 21-27. crossref(new window)

Park, J., Shim, M., Rhyu, M. R. and Lee, Y. 2012. Estrogen receptor mediated effects of Cimicifuga extracts on human breast cancer cells. Pharmazie. 67, 947-950.

Park, S. J. and Kim, S. K. 2010. Anti-inflammatory Effects of Belamcanda chinensis Water Extract. Kor. J. Ori. Physiol. Pathol. 24, 410-415.

Ríos, J. L. 2011. Chemical constituents and pharmacological properties of Poria cocos. Planta Med. 77, 681-691. crossref(new window)

Scorrano, L. and Korsmeyer, S. J. 2003. Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochem. Biophys. Res. Commun. 304, 437-444. crossref(new window)

Shamas-Din, A., Brahmbhatt, H., Leber, B. and Andrews, D. W. 2011. BH3-only proteins: Orchestrators of apoptosis. Biochim. Biophys. Acta. 1813, 508-520. crossref(new window)

Tomek, M., Akiyama, T. and Dass, C. R. 2012. Role of Bcl-2 in tumour cell survival and implications for pharmacotherapy. J. Pharm. Pharmacol. 64, 1695-1702. crossref(new window)

Walczak, H. and Krammer, P. H. 2000. The CD95 (APO-1/Fas) and the TRAIL (APO-2L) apoptosis systems. Exp. Cell Res. 256, 58-66. crossref(new window)

Zhang, W. and Dai, S. M. 2012. Mechanisms involved in the therapeutic effects of Paeonia lactiflora Pallas in rheumatoid arthritis. Int. Immunopharmacol. 14, 27-31. crossref(new window)