Effects of polysaccharides derived from Orostachys japonicus on induction of cell cycle arrest and apoptotic cell death in human colon cancer cells
2
조회
0
다운로드
14
인용
0
참고문헌
키워드
초록
Crude Orostachys japonicus polysaccharide extract (OJP) was prepared by hot steam extraction. Polysaccharides (OJPI) were separated from OJP by gel filtration chromatography and phenol-sulfuric acid assay. The average molecular weight of the OJPI was 30-50 kDa. The anti-proliferative effect of OJPI on HT-29 human colon cancer cells was investigated via morphology study, cell viability assay, apoptosis assay, cell cycle analysis, and cDNA microarray. OJPI inhibited proliferation and growth of HT29 cells and also stimulated apoptosis in a dose- and time-dependent manner. In cell cycle analysis, treatment with OJPI resulted in a marked increase of cells in the G0 (sub G1) and G2/M phases. To screen for genes involved in the induction of cell cycle arrest and apoptosis, the gene expression profiles of HT-29 cells treated with OJPI were examined by cDNA microarray, revealing that a number of genes were up- or down-regulated by OJPI. Whereas several genes involved in anti-apoptosis, cell proliferation and growth, and cell cycle regulation were down-regulated, expression levels of several genes involved in apoptosis, tumor suppression, and other signal transduction events were up-regulated. These results suggest that OJPI inhibits the growth of HT-29 human colon cancer cells by various apoptosis-aiding activities as well as apoptosis itself. Therefore, OJPI deserve further development as an effective agent exhibiting anticancer activity.
Abstract
Crude Orostachys japonicus polysaccharide extract (OJP) was prepared by hot steam extraction. Polysaccharides (OJPI) were separated from OJP by gel filtration chromatography and phenol-sulfuric acid assay. The average molecular weight of the OJPI was 30-50 kDa. The anti-proliferative effect of OJPI on HT-29 human colon cancer cells was investigated via morphology study, cell viability assay, apoptosis assay, cell cycle analysis, and cDNA microarray. OJPI inhibited proliferation and growth of HT29 cells and also stimulated apoptosis in a dose- and time-dependent manner. In cell cycle analysis, treatment with OJPI resulted in a marked increase of cells in the G0 (sub G1) and G2/M phases. To screen for genes involved in the induction of cell cycle arrest and apoptosis, the gene expression profiles of HT-29 cells treated with OJPI were examined by cDNA microarray, revealing that a number of genes were up- or down-regulated by OJPI. Whereas several genes involved in anti-apoptosis, cell proliferation and growth, and cell cycle regulation were down-regulated, expression levels of several genes involved in apoptosis, tumor suppression, and other signal transduction events were up-regulated. These results suggest that OJPI inhibits the growth of HT-29 human colon cancer cells by various apoptosis-aiding activities as well as apoptosis itself. Therefore, OJPI deserve further development as an effective agent exhibiting anticancer activity.
참고문헌 (29)
- Je, M., "Calpain inhibitory flavonoids isolated from Orostachys japonicus", J. Enzyme Inhib. Med. Chem., 24, pp.676~679 (2009)
- Park, H. J., "Flavonoids from the whole plants of Orostachys japonicus", Arch. Pharm. Res., 14, pp.167~171 (1991)
- Yoon, Y., "Protective effects of Orostachys japonicus A. Berger (Crossuloceae) on H2O2 - induced apoptosis in GTI-1 mouse hypothalamic neuronal cell line", J. Ethnopharmacol., 69, pp.73~78 (2000)
- Na Young Yoon, "A Potent Anti-Complementary Acylated Sterol Glucoside from Orostachys japonicus", Archives of Pharmacal Research, 28(8), pp.892~896 (2005), 대한약학회
- Jemal, A., "Cancer statistics", Cancer J. Clin., 59, pp.225~249 (2009)
- Chau, I., "Adjuvant therapy in colon cancer - What, when and how?", Ann. Oncol., 17, pp.1347~1359 (2006)
- Kelloff, G. J., "Perspectives on cancer chemoprevention research and drug development", Adv. Cancer Res., 78, pp.199~334 (2000)
- 류덕선, "Anti-Proliferative Effect of Polysaccharides from Salicornia herbacea on Induction of G2", M Arrest and Apoptosis in Human Colon Cancer Cells, 2009, pp.19(11), 1482~1489[DOI]
- Kaina, B., "DNA damage - triggered apoptosis: critical role of DNA repair, double - strand breaks, cell proliferation and signaling", Biochem. Pharmacol., 66, pp.1547~1554 (2003)
- 김기훈, "와송 다당체 및 올리고당류의 생리 활성", 미생물학회지, 40(4), pp.334~341 (2004), 한국미생물학회
- NAM, KYUNG-SOO, "Chemopreventive Effect of Chitosan Oligosaccharide Against Colon Carcinogenesis", Journal of Microbiology and Biotechnology, 17(9), pp.1546~1549 (2007), 한국미생물·생명공학회
- Hyun, J. H., "Apoptosis inducing activity of fucoidan in HCT-15 colon carcinoma cells", Biol. Pharm. Bull., 32, pp.1760~1764 (2009)
- Bao, H. H., "Effect of sulfated modification on the molecular characteristics and biological activities of polysaccharides from Hypsizigus marmoreus", Biosci. Biotechnol. Biochem., 74, pp.1408~1414 (2010)
- Arends, M. J., "Apoptosis in the endometrium", Mistopathology, 35, pp.174~178 (1999)
- Boukes, G. J., "Cell survival or apoptosis: rooperol’s role as anticancer agent", Oncol. Res., 18, pp.365~376 (2010)
- Soule, B. P., "Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines", Radiat. Oncol., 5, pp.1~12 (2010)
- Yang, E., "Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death", Cell, 80, pp.285~291 (1995)
- Zhang, J. K., "Fas - mediated apoptosis and activation - induced T-cell proliferation are defective in mice lacking FADD", Mort 1, 1998, pp.392, 296~300
- Liu, C., "Antisense oligonucleotide targeting Livin induces apoptosis of human bladder cancer cell via a mechanism involving caspase3", J. Exp. Clin. Cancer Res., 29, pp.1~8 (2010)
- Naumovski, L., "The p53 - binding protein 53BP2 also interacts with Bc1-2 and impedes cell cycle progression at G2", M, 1996, pp.16, 3884~3892
- Kimura, H. J., "Influence of signal transducer and activator of transcription- 1 Signaling on thyroid morphology and function", Endocrinology, 150, pp.3409~3416 (2009)
- Lee, S. T., "A survey of protein tyrosin kinase mRNAs expressed in normal human melanocytes", Oncogene., 8, pp.3403~3410 (1993)
- Gibson, L., "Bcl-w, a novel member of the bcl-2 family, promotes cell survival", Oncogene., 15, pp.665~675 (1996)
- Naiki, T., "Rfc5, in cooperation with rad 24, controls DNA damage checkpoints throughout the cell cycle in Saccharomyces cerevisiae", Mol. cell Biol., 20, pp.5888~5896 (2000)
- Buhling, F., "Expression of cathepsins B, H, K, L, and S during human fetal lung development", Dev. Dyn., 225, pp.14~21 (2002)
- Klarzynski, O., "Linear beta - 1, 3 glucans are elicitors of defense responses in tobacco", Plant Physiol., 124, pp.1027~1038 (2000)
- Cuesta, G., "Quantitative determination of pneumococcal capsular polysaccharide serotype 14 using a modification of phenol - sulfuric acid method", J. Microbiol. Methods., 52, pp.69~73 (2003)
- Eray, M., "Flow cytometric analysis of apoptotic subpopulations with a combination of annexin V-FITC, propidium iodide, and SYTO 17", Cytometry, 43, pp.134~142 (2001)
- Kim, K. H., "Anti - apoptotic activity of laminarin polysaccharides and their enzymatically hydrolyzed oligosaccharides from Laminaria Joponica", Biotechnol. Lett., 28, pp.439~446 (2006)