Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Over-expression of NSAID Activated Gene-1 by Caffeic Acid Phenethyl Ester

Caffeic acid phenethyl ester의 처리에 의한 NSAID activated gene-1의 과대발현

  • Jang, Min-Jeong (Dept. of Biological Sciences, Andong National University) ;
  • Kim, Hyo-Eun (Dept. of Biological Sciences, Andong National University) ;
  • Son, Seong-Min (Dept. of Biological Sciences, Andong National University) ;
  • Kim, Min-Jeong (Dept. of Biological Sciences, Andong National University) ;
  • Seo, Eul-Won (Dept. of Biological Sciences, Andong National University) ;
  • Kim, Young-Ho (Dept. of Microbiology, Kyungpook National University) ;
  • Kim, Jong-Sik (Dept. of Biological Sciences, Andong National University)
  • 장민정 (안동대학교 자연과학대학 생명과학과) ;
  • 김효은 (안동대학교 자연과학대학 생명과학과) ;
  • 손성민 (안동대학교 자연과학대학 생명과학과) ;
  • 김민정 (안동대학교 자연과학대학 생명과학과) ;
  • 서을원 (안동대학교 자연과학대학 생명과학과) ;
  • 김영호 (경북대학교 자연과학대학 미생물학과) ;
  • 김종식 (안동대학교 자연과학대학 생명과학과)
  • Published : 2009.12.30
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Abstract

To investigate whether caffeic acid phenethyl ester (CAPE) could affect cancer cell viabilities and gene expression, human colorectal HCT116 cells were incubated with CAPE. CAPE decreased cancer cell viabilities and induced apoptosis in a dose-dependent manner. To analyse differently expressed genes by CAPE, we performed oligo DNA microarray analysis. We found that 266 genes were up-regulated more than twofold, whereas 143 genes were down-regulated more than twofold by 24 hr of treatment with $20{\mu}M$ CAPE. Among the up-regulated genes, we selected 3 genes (NSAID activated gene-1 [NAG-1], cyclin-dependent kinase inhibitor 1A [CDKN1A, p21] and growth arrest and DNA-damage-inducible alpha [GADD45A]) and performed reverse-transcription PCR to confirm microarray data. In addition, we found that CAPE increased NAG-1 gene and NAG-1 protein expression in a dose-dependent manner. And, several other phytochemicals (resveratrol, genistein, daidzein and capsaicin) also could induce NAG-1 expression in human colorectal HCT116 cells. However, CAPE was the highest inducer of NAG-1, even in low concentrations. Overall, these results imply that cancer cell death by CAPE is closely related with over-expression of NAG-1.

파이토케미칼의 일종인 CAPE가 암세포 생장에 미치는 영향과 유전자 발현을 연구하기 위하여, 인간 대장암 세포주 HCT116에 CAPE를 처리하였다. CAPE의 처리는 농도 의존적으로 암 세포 생존율을 감소시키고, 세포사멸을 유도함을 확인하였다. CAPE에 의해 차별적으로 발현되는 유전자를 분석하기 위하여, oligo DNA microarray 실험을 수행하였다. 그 결과, $20{\mu}M$ CAPE를 24시간 동안 처리한 경우, 2배 이상 발현이 증가되는 유전자 266개, 2배 이상 발현이 감소되는 유전자 143개를 확인하였다. 발현이 증가되는 유전자중 3개(NAG-1, p21, GADD45A)를 선택하여, RT-PCR을 수행하였다. 그 결과, 모든 유전자의 발현이 마이크로어레이 실험결과와 일치하였다. 또한, CAPE를 농도 의존적으로 처리한 후, NAG-1 유전자와 단백질의 발현을 확인한 결과, mRNA 수준과 단백질 수준에서의 발현양상이 동일함을 확인하였다. 게다가, CAPE를 포함한 5개의 다른 종류의 파이토케미칼(resveratrol, genistein, daidzein, capsaicin)을 처리한 경우, 처리한 모든 파이토케미칼에 의해 NAG-1 유전자의 발현이 증가됨을 확인하였다. 이중 CAPE가 가장 낮은 농도의 처리임에도 불구하고 NAG-1의 발현을 가장 강하게 유도하였다. 결론적으로 이러한 연구결과는 CAPE에 의한 세포사멸은 항암유전자인 NAG-1의 과대발현과 밀접한 관련이 있음을 의미한다.

Keywords

References

  1. Baek, S. J., J. S. Kim, J. B. Nixon, L. C. Wilson, and T. E. Eling. 2001. Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities. Mol. Pharmacol. 59, 901-908
  2. Baek S. L. J., L. C. Wilson, and T. E. Eling. 2002. Resveratrol enhances the expression of non-steroidal anti-inflammatory drug-activated gene (NAG-I) by increasing the expression of p53. Carcinogenesis 23, 425-434 https://doi.org/10.1093/carcin/23.3.425
  3. Baek, S. J., R. Okazaki, S. H. Lee, J. Martinez, J. S. Kim, K. Yamaguchi, Y. Mishina, D. W. Martin, A. Shoieb, M. F. McEntee, and T. E. Eling. 2006. Nonsteroidal anti-inflammatory drug-activated gene-lover expression in transgenic mice suppresses intestinal neoplasia. Gastroenterology 131, 1553-1560 https://doi.org/10.1053/j.gastro.2006.09.015
  4. Chen, Y. J., M. S. Shiao, and S. Y. Wang. 2001. The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells. Anticancer Drugs 12, 143-149 https://doi.org/10.1097/00001813-200102000-00008
  5. Chen, M. J., W. H. Chang, C. C. Lin, C. Y. Liu, T. E. Wang, C. H. Chu, S. C. Shih, and Y. J. Chen. 2008. Caffeic acid phenethyl ester induces apoptosis of human pancreatic cancer cells involving caspase and mitochondrial dysfunction. Pancreatology 8, 566-576 https://doi.org/10.1159/000159843
  6. Corn, P. G. and W. S. El-Deiry. 2007. Microarray analysis of p53-dependent gene expression in response to hypoxia and DNA damage. Cancer BioI. Ther. 6, 1858-1866 https://doi.org/10.4161/cbt.6.12.5330
  7. Fesen, M. R., Y. Pommier, F. Leteurtre, S. Hiroguchi, J. Yung, and K. W. Kohn. 1994. Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds. Biochem. Pharmacol. 48, 595-608 https://doi.org/10.1016/0006-2952(94)90291-7
  8. Foo, E., E. Bullier, M. Goussot, F. Foucher, C. Rameau, and C. A. Beverideg. 2005. The branching gene RAMOSUS1 mediates interactions among two novel signals and auxin in pea. Plant Cell 17, 464-474 https://doi.org/10.1105/tpc.104.026716
  9. He, Y. J., B. H. Liu, D. B. Xiang, Z. Y. Qiao, T. Fu, and Y. H. He. 2006. Inhibitory effect of caffeic acid phenethyl ester on the growth of SW 480 colorectal tumor cells involves beta-catenin associated signaling pathway down-regulation. World J. Gastroenterol. 12, 4981-4985
  10. Jacobs, D. R Jr, L. Marquart, J. Slavin, and L. H. Kushi. 1998. Whole-grain intake and cancer: an expanded review and meta-analysis. Nutr. Cancer 30, 85-96 https://doi.org/10.1080/01635589809514647
  11. Jin, U. H., K. H. Song, M. Motomura, I. Suzuki, Y. H. Gu, Y. J. Kang, T. C. Moon, and C. H. Kim. 2008. Caffeic acid phenethyl ester induces mitochondria-mediated apoptosis in human myeloid leukemia U937 cells. Mol. Cell Biochem. 310, 43-48 https://doi.org/10.1007/s11010-007-9663-7
  12. Jung, W. K., I. Choi, D. Y. Lee, S. S. Yea, Y. H. Choi, M. M. Kim, S. G. Park, S. K. Seo, S. W. Lee, C. M. Lee, Y. M. Park, and I. W. Choi. 2008. Caffeic acid phenethyl ester protects mice from lethal endotoxin shock and inhibits lipopolysaccharide-induced cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW 264.7 macrophages via the p38/ERK and NF-kappaB pathways. Int. J. Biochem. Cell BioI. 40, 2572-2582 https://doi.org/10.1016/j.biocel.2008.05.005
  13. Kuo, H. C., W. H. Kuo, Y. J. Lee, W. L. Lin, F. P. Chou, and T. H Tseng. 2006. Inhibitory effect of caffeic acid phenethyl ester on the growth of C6 glioma cells in vitro and in vivo. Cancer Lett. 234, 199-208 https://doi.org/10.1016/j.canlet.2005.03.046
  14. Lampe, J. W. and J. L. Chang. 2007. Interindividual differences in phytochemical metabolism and disposition. Semin. Cancer BioI. 17, 347-353 https://doi.org/10.1016/j.semcancer.2007.05.003
  15. Lee, K. W., N. J. Kang, J. H Kim, K. M. Lee, D. E. Lee, H. J. Hur, and H. J. Lee. 2008. Caffeic acid phenethyl ester inhibits invasion and expression of matrix metalloproteinase in SK-Hep1 human hepatocellular carcinoma cells by targeting nuclear factor kappa B. Genes Nutr. 2, 319-322 https://doi.org/10.1007/s12263-007-0067-9
  16. Maekawa, T, Y. Sano, T. Shinagawa, Z. Rahman, T. Sakuma, S. Nomura, J. D. Licht, and S. Ishii. 2008. ATF-2 controls transcription of Maspin and GADD45 alpha genes independently from p53 to suppress mammary tumors. Oncogene 27, 1045-1054 https://doi.org/10.1038/sj.onc.1210727
  17. Michaluart, P, J. L. Masferrer, A. M. Carothers, K. Subbaramaiah, B. S. Zweife, C. C. Koboldt, J. R. Mestre, D. Grunberger, P. G. Sacks, T. Tanabe, and A. J. Dannenberg. 1999. Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Res. 59, 2347-2352
  18. Rahman, K. W., Y. Li, Z. Wang, S. H Sarkar, and F. H. Sarkar. 2006. Gene expression profiling revealed survivin as a target of 3,3' -diindolylmethane-induced cell growth inhibition and apoptosis in breast cancer cells. Cancer Res. 66, 4952-4960 https://doi.org/10.1158/0008-5472.CAN-05-3918
  19. Schena, M., D. Shalon, R. W. Davis, and P. O. Brown. 1995. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270, 467-470 https://doi.org/10.1126/science.270.5235.467
  20. Sun, S. Y, N. Hail Jr, and R Lotan. 2004. Apoptosis as a novel target for cancer chemoprevention. J. Natl. Cancer Inst. 96, 662-672 https://doi.org/10.1093/jnci/djh123
  21. Surh, Y. J. 2003. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer 3, 768-780 https://doi.org/10.1038/nrc1189
  22. Takahashi, Y, J. A. Lavigne, S. D. Hursting, G. V. Chandramouli, S. N. Perkins, J. C. Barrett, and T. T. Wang. 2004. Using DNA microarray analyses to elucidate the effects of genistein in androgen-responsive prostate cancer cells: identification of novel targets. Mol. Carcinog. 41, 108-119 https://doi.org/10.1002/mc.20045
  23. Wang, D, D. B. Xiang, Y J. He, Z. P. Li, X. H Wu, J. H. Mou, H. L. Xiao, and Q. H. Zhang. 2005. Effect of caffeic acid phenethyl ester on proliferation and apoptosis of colorectal cancer cells in vitro. World J. Gastroenterol. 11, 4008-4012
  24. Wilson, L. C., S. J. Baek, A. Call, and T. E. Eling. 2003. Nonsteroidal anti-inflammatory drug-activated gene (NAG-1) is induced by genistein through the expression of p53 in colorectal cancer cells. Int. J. Cancer 105, 747-753 https://doi.org/10.1002/ijc.11173
  25. Xiang, D., D. Wang, Y. He, J. Xie, Z. Zhong, Z. Li, and J. Xie. 2006. Caffeic acid phenethyl ester induces growth arrest and apoptosis of colon cancer cells via the beta-catenin/T-cell factor signaling. Anticancer Drugs 17, 753-762 https://doi.org/10.1097/01.cad.0000224441.01082.bb

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