- Volume 21 Issue 6
DOI QR Code
Sulforaphane-Induced Apoptosis was Regulated by p53 and Caspase-3 Dependent Pathway in Human Chondrosarcoma, HTB-94
Sulforaphane에 의한 p53 및 caspase-3 의존 신호전달계를 통한 인간 연골암 세포주 HTB-94에서의 세포사멸 기전 연구
- Received : 2011.04.01
- Accepted : 2011.05.26
- Published : 2011.06.30
Sulforaphane (SFN) is an isothiocyanate, isolated from glucoraphanin in broccoli and other cruciferaous vegetables. Recent studies have revealed that SFN induces anti-proliferation and apoptosis by cell cycle arrest in various cancer cells. In this study, we investigated the effect of SFN induced apoptosis in chondrosarcoma HTB-94 cells. SFN caused suppression of proliferation and apoptosis in a dose-dependent manner as determined by cell phenotype, MTT assay and FACS analysis in HTB-94 cells. Treatment of SFN led to caspase-3 activation and p53 accumulation as determined by Western blot analysis. Also, SFN significantly induced DNA fragmentation and nuclear degradation though activation of caspase-3, as detected by DNA electrophoresis and immunostaining, respectively. Our results indicate that SFN-induced apoptosis was regulated by p53 and caspase-3 dependent pathways. Furthermore, SFN may act as a potent anti-proliferation agent, and as a promising candidate for molecular-targeting chemotherapy against human chondrosarcoma cells.
- Bar, J., N. Moskovits, and M. Oren. 2010. Involvement of stromal p53 in tumor-stroma interactions. Semin. Cell Dev. Biol. 21, 47-54. https://doi.org/10.1016/j.semcdb.2009.11.006
- Boulon, S., B. J. Westman, S. Hutten, F. M. Boisvert, and A. I. Lamond. 2010. The nucleolus under stress. Mol. Cell 40, 216-227. https://doi.org/10.1016/j.molcel.2010.09.024
- Brooks, J. D., V. G. Paton, and G. Vidanes. 2001. Potent induction of phase 2 enzymes in human prostate cells by sulforaphane. Cancer Epidemiol. Biomarkers Prev. 10, 949-954.
- Cho, S. D., G. Li, H. Hu, C. Jiang, K. S. Kang, Y. S. Lee, S. H. Kim, and J. Lu. 2005. Involvement of c-Jun N-terminal kinase in G2/M arrest and caspase-mediated apoptosis induced by sulforaphane in DU145 prostate cancer cells. Nutr. Cancer 52, 213-224. https://doi.org/10.1207/s15327914nc5202_11
- Chung, F. L., C. C. Conaway, C. V. Rao, and B. S. Reddy. 2000. Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis 21, 2287-2291. https://doi.org/10.1093/carcin/21.12.2287
- Gamet-Payrastre, L., P. Li, S. Lumeau, G. Cassar, M. A. Dupont, S. Chevolleau, N. Gasc, J. Tulliez, and F. Terce. 2000. Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res. 60, 1426-1433.
- Hecht, S. S. 1995. Chemoprevention by isothiocyanates. J. Cell Biochem. Suppl. 22, 195-209.
- Herman-Antosiewicz, A., D. E. Johnson, and S. V. Singh. 2006. Sulforaphane causes autophagy to inhibit release of cytochrome C and apoptosis in human prostate cancer cells. Cancer Res. 66, 5828-5835. https://doi.org/10.1158/0008-5472.CAN-06-0139
- Herman-Antosiewicz, A., H. Xiao, K. L. Lew, and S. V. Singh. 2007. Induction of p21 protein protects against sulforaphane- induced mitotic arrest in LNCaP human prostate cancer cell line. Mol. Cancer Ther. 6, 1673-1681. https://doi.org/10.1158/1535-7163.MCT-06-0807
Kim, J. H., K. Han Kwon, J. Y. Jung, H. S. Han, J. Hyun Shim, S. Oh, K. H. Choi, E. S. Choi, J. A. Shin, D. H. Leem, Y. Soh, N. P. Cho, and S. D. Cho. 2010. Sulforaphane increases cyclin-dependent kinase inhibitor, p21 protein in human oral carcinoma cells and nude mouse animal model to induce
$G(_2)/M$cell cycle arrest. J. Clin. Biochem. Nutr. 46, 60-67.
- Kim, S. J., S. G. Hwang, I. C. Kim, and J. S. Chun. 2003. Actin cytoskeletal architecture regulates nitric oxide-induced apoptosis, dedifferentiation, and cyclooxygenase-2 expression in articular chondrocytes via mitogen-activated protein kinase and protein kinase C pathways. J. Biol. Chem. 278, 42448-42456. https://doi.org/10.1074/jbc.M304887200
- Kim, S. J., J. W. Ju, C. D. Oh, Y. M. Yoon, W. K. Song, J. H. Kim, Y. J. Yoo, O. S. Bang, S. S. Kang, and J. S. Chun. 2002. ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status. J. Biol. Chem. 277, 1332-1339. https://doi.org/10.1074/jbc.M107231200
- Mi, L., N. Gan, A. Cheema, S. Dakshanamurthy, X. Wang, D. C. Yang, and F. L. Chung. 2009. Cancer preventive isothiocyanates induce selective degradation of cellular alphaand beta-tubulins by proteasomes. J. Biol. Chem. 284, 17039-17051. https://doi.org/10.1074/jbc.M901789200
- Mi, L., Z. Xiao, B. L. Hood, S. Dakshanamurthy, X. Wang, S. Govind, T. P. Conrads, T. D. Veenstra, and F. L. Chung. 2008. Covalent binding to tubulin by isothiocyanates. A mechanism of cell growth arrest and apoptosis. J. Biol. Chem. 283, 22136-22146. https://doi.org/10.1074/jbc.M802330200
- Misiewicz, I., K. Skupinska, and T. Kasprzycka-Guttman. 2003. Sulforaphane and 2-oxohexyl isothiocyanate induce cell growth arrest and apoptosis in L-1210 leukemia and ME-18 melanoma cells. Oncol. Rep. 10, 2045-2050.
- Myzak, M. C. and R. H. Dashwood. 2006. Chemoprotection by sulforaphane: keep one eye beyond Keap1. Cancer Lett. 233, 208-218. https://doi.org/10.1016/j.canlet.2005.02.033
- Park, S. Y., G. Y. Kim, S. J. Bae, Y. H. Yoo, and Y. H. Choi. 2007. Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3. Oncol. Rep. 18, 181-187.
- Parnaud, G., P. Li, G. Cassar, P. Rouimi, J. Tulliez, L. Combaret, and L. Gamet-Payrastre. 2004. Mechanism of sulforaphane-induced cell cycle arrest and apoptosis in human colon cancer cells. Nutr. Cancer 48, 198-206. https://doi.org/10.1207/s15327914nc4802_10
- Pham, N. A., J. W. Jacobberger, A. D. Schimmer, P. Cao, M. Gronda, and D. W. Hedley. 2004. The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice. Mol. Cancer. Ther. 3, 1239-1248.
- Pledgie-Tracy, A., M. D. Sobolewski, and N. E. Davidson. 2007. Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. Mol. Cancer. Ther. 6, 1013-1021.
- Qazi, A., J. Pal, M. Maitah, M. Fulciniti, D. Pelluru, P. Nanjappa, S. Lee, R. B. Batchu, M. Prasad, C. S. Bryant, S. Rajput, S. Gryaznov, D. G. Beer, D. W. Weaver, N. C. Munshi, R. K. Goyal, and M. A. Shammas. 2010. Anticancer activity of a broccoli derivative, sulforaphane, in barrett adenocarcinoma: potential use in chemoprevention and as adjuvant in chemotherapy. Transl. Oncol. 3, 389-399. https://doi.org/10.1593/tlo.10235
- Roy, S. K., R. K. Srivastava, and S. Shankar. 2010. Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer. J. Mol. Signal 5, 10. https://doi.org/10.1186/1750-2187-5-10
- Rudolf, E., H. Andelova, and M. Cervinka. 2009. Activation of several concurrent proapoptic pathways by sulforaphane in human colon cancer cells SW620. Food Chem. Toxicol. 47, 2366-2373. https://doi.org/10.1016/j.fct.2009.06.034
- Singh, A. V., D. Xiao, K. L. Lew, R. Dhir, and S. V. Singh. 2004. Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis 25, 83-90.
- Singh, S. V., A. Herman-Antosiewicz, A. V. Singh, K. L. Lew, S. K. Srivastava, R. Kamath, K. D. Brown, L. Zhang, and R. Baskaran. 2004. Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C. J. Biol. Chem. 279, 25813-25822. https://doi.org/10.1074/jbc.M313538200
- Tang, L., Y. Zhang, H. E. Jobson, J. Li, K. K. Stephenson, K. L. Wade, and J. W. Fahey. 2006. Potent activation of mitochondria- mediated apoptosis and arrest in S and M phases of cancer cells by a broccoli sprout extract. Mol. Cancer Ther. 5, 935-944. https://doi.org/10.1158/1535-7163.MCT-05-0476
- Zhang, Y., T. W. Kensler, C. G. Cho, G. H. Posner, and P. Talalay. 1994. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc. Natl. Acad. Sci. USA 91, 3147-3150. https://doi.org/10.1073/pnas.91.8.3147
- Zielinski, C. C., T. Brodowicz, C. Wiltschke, D. Kandioler-Eckersberger, T. W. Grunt, M. Rudas, S. M. Schneider, M. Hejna, and A. Budinsky. 1999. Inhibition of proliferation and induction of apoptosis in soft tissue sarcoma cells by interferon-a and retinoids. British J. Cancer 80, 1350-1358. https://doi.org/10.1038/sj.bjc.6690528
- Inhibition of Cell Proliferation and Induction of Apoptosis by Ethanolic Extract of Lespedeza cuneata G. Don in Human Colorectal Cancer HT-29 cells vol.45, pp.6, 2016, https://doi.org/10.3746/jkfn.2016.45.6.911
- Apoptotic Effects and Cell Cycle Arrest Effects of Extracts from Cnidium monnieri (L.) Cusson through Regulating Akt/mTOR/GSK-3β Signaling Pathways in HCT116 Colon Cancer Cells vol.26, pp.6, 2016, https://doi.org/10.5352/JLS.2016.26.6.663
- Apoptotic effects of extract from Cnidium monnieri (L.) Cusson by adenosine monosphosphate-activated protein kinase-independent pathway in HCT116 colon cancer cells vol.13, pp.6, 2016, https://doi.org/10.3892/mmr.2016.5115
Supported by : 한국연구재단