Induction of Apoptosis of DK-5-62, a Novel (-)-Catechin Derivative Through MAPKs Signaling Pathway in HCT116 Cells
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The present study was designed to investigate the molecular mechanisms of DK-5-62, a novel (-)-catechin derivative on HCT116 human colorectal cancer cells. DK-5-62 inhibited the proliferation in dose- and time-dependent manner accompanied by the morphological changes. Effects of DK-5-62 appeared to be mediated by the induction of apoptosis, as manifested through DNA-binding dye Hoechst 33258 staining. Analysis of the mechanism of these events indicated that DK- 5-62-treated cells exhibited an increased ratio of Bax/Bcl-2, resulting in the activation of caspase-9, caspase-3, and poly-ADPribose polymerase in a dose-dependent manner. Moreover, DK-5-62-induced apoptosis was accompanied by phosphorylation of the mitogen-activated protein kinase family, c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase. These results suggest that HCT116 cells are moderately sensitive to growth inhibition by DK-5-62 via apoptosis, as evidenced by activation of ERK/p38/Bcl-2 family signaling, as well as alteration in caspase-9 and caspase-3.
Abstract
The present study was designed to investigate the molecular mechanisms of DK-5-62, a novel (-)-catechin derivative on HCT116 human colorectal cancer cells. DK-5-62 inhibited the proliferation in dose- and time-dependent manner accompanied by the morphological changes. Effects of DK-5-62 appeared to be mediated by the induction of apoptosis, as manifested through DNA-binding dye Hoechst 33258 staining. Analysis of the mechanism of these events indicated that DK- 5-62-treated cells exhibited an increased ratio of Bax/Bcl-2, resulting in the activation of caspase-9, caspase-3, and poly-ADPribose polymerase in a dose-dependent manner. Moreover, DK-5-62-induced apoptosis was accompanied by phosphorylation of the mitogen-activated protein kinase family, c-Jun N-terminal kinase, p38, and extracellular signal-regulated kinase. These results suggest that HCT116 cells are moderately sensitive to growth inhibition by DK-5-62 via apoptosis, as evidenced by activation of ERK/p38/Bcl-2 family signaling, as well as alteration in caspase-9 and caspase-3.
참고문헌 (37)
- Leah, H.B., , JAMA, 7, pp.669~ (2021)
- Johnson, J. J., , Cancer Lett, 255, pp.170~ (2007)
- Portt, L., , Biochim. Biophys. Acta, 1813, pp.238~ (2011)
- Wang, X., , Genes Dev, 15, pp.2922~ (2001)
- Reuter, S., , Biochem. Pharmacol, 76, pp.1340~ (2008)
- Green, D. R., , Sci, 281, pp.1309~ (1998)
- Madesh, M., , J. Biol. Chem, 277, pp.5651~ (2002)
- Fernandes-Alnemri, T., , J. Biol. Chem, 269, pp.30761~ (1994)
- Zorov, D. B., , Physio. Rev, 94, pp.909~ (2014)
- Park, M., , J. Nutr, 141, pp.1862~ (2011)
- Deepak Kumar, "Antimicrobial and docking studies of (2)-catechin derivatives", Applied Biological Chemistry, 58(4), pp.581~585 (2015), 한국응용생명화학회
- Sitheeque, M. A., , Chemotherapy, 55, pp.189~ (2009)
- Suganuma, M., , Cancer Sci, 102, pp.317~ (2011)
- Musial, C., , Int. J. Mol. Sci, 21, pp.1744~ (2020)
- Khan, S. T., , Neurochem. Int, 149, pp.105135~ (2021)
- Okello, E. J., , Nutrients, 12, pp.1090~ (2020)
- Kashif, M., , Cell. Mol. Biol, 67, pp.132~ (2021)
- Deepak Kumar, "Design, Synthesis In Vitro Anticancer Activity and Docking Studies of (−)-Catechin Derivatives", Bulletin of the Korean Chemical Society, 36(2), pp.564~570 (2015), 대한화학회[DOI]
- Deepak Kumar, "Synthesis, Antioxidant and Molecular Docking Studies of (?)-Catechin Derivatives", 대한화학회지, 65(2), pp.106~112 (2021), 대한화학회
- Carmichael, J., , Cancer Res, 47, pp.936~ (1987)
- Gschwind, M., , J. Neurochem, 65, pp.292~ (1995)
- Lizard, G., , Cytometry, 21, pp.275~ (1995)
- Ryu, M. J., , In Vitro Cell. Dev. Biol. Anim, 51, pp.92~ (2015)
- Lee, S. -H., , Cell Death Differ, 20, pp.64~ (2013)
- Darbre, P. D., , J. Appl. Toxicol, 34, pp.925~ (2014)
- Ryu, M. J., , In Vitro Cell. Dev. Biol. Anim, 49, pp.74~ (2013)
- Nagappan, A., , Food Chem, 135, pp.1920~ (2012)
- Sun, L., , Mol, 20, pp.3758~ (2015)
- Li, P., , Cell, 91, pp.479~ (1997)
- Acehan, D., , Mol. Cell, 9, pp.423~ (2002)
- Trebinska, A., , FEBS Lett, 588, pp.2921~ (2014)
- Liu, X., , Mol. Med. Rep, 12, pp.1183~ (2015)
- Kim, E. K., , Arch. Toxicol, 89, pp.867~ (2015)
- Ahmed-Choudhury, J., , Cell. Signal, 18, pp.456~ (2006)
- Boldt, S., , Carcinogen, 23, pp.1831~ (2002)
- Thanikachalam, K., , Nutrients, 11, pp.164~ (2019)
- Wang, D., , Oncogene, 29, pp.781~ (2010)