Abstract
The study aimed to evaluate the effects of deoxycholic acid (DCA) on human gastric carcinoma cell lines and to explore its mechanisms. In the present study, effects of DCA on SGC-7901 cell growth, cell cycle, and apoptosis were investigated by MTT assay, inverted microscopy, fluorescence microscopy, PI single- and FITC/PI double-staining flow cytometry, and western blotting. The study have revealed that DCA significantly inhibited the growth of SGC-7901 cells in a dose- and time-dependent manner and arrested cell cycle at G0/G1 phase. SGC-7901 cells showed typical apoptotic morphological changes after treated with DCA for 48 h. The intensity of typical apoptosis pattern- “ladders” formed by DNA in fragments of multiples of 200 base pairs was also observed. Apoptosis of SGC-7901 cells induced by DCA were associated with collapse of the mitochondrial membrane potential. DCA treatment could also increase the ratio of Bax to Bcl-2 in SGC-7901 cells. Meanwhile, the expression of p53, cyclinD1, and c-Myc were changed after DCA treatment. These results suggest that DCA induces apoptosis of gastric carcinoma cells through an intrinsic mitochondrial-dependent pathway, and the increase in the Bax/Bcl-2 ratio and collapse of the mitochondrial membrane potential may play important roles in DCA-induced apoptosis of gastric carcinoma cells.
Similar content being viewed by others
Abbreviations
- DCA:
-
Deoxycholic acid
- ROS:
-
Reactive oxygen species
- PI:
-
Propidium iodide
- FBS:
-
Fetal bovine serum
- MTT:
-
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
- HRP:
-
Horseradish peroxidase
- ECL:
-
Enhanced chemiluminescence
References
Hartgrink, H. H., Jansen, E. P., Grieken, N., & Velde, C. (2009). Lancet (British edition), 374(9688), 477–490.
Roder, D. M. (2002). Gastric cancer, 5(1), 5–11.
Coupland, V. H., Allum, W., Blazeby, J. M., Mendall, M. A., Hardwick, R. H., Linklater, K. M., et al. (2012). BMC Cancer, 12, 11.
Gordaliza, M. (2008). Clinical and Translational Oncology, 9(12), 767–776.
Newman, D. J., & Cragg, G. M. (2007). Journal of natural products, 70(3), 461–477.
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009). Physiological reviews, 89(1), 147–191.
Im, E.-o., Choi, Y. H., Paik, K.-J., Suh, H., Jin, Y., Kim, K.-W., et al. (2001). Cancer Letters, 163(1), 83–93.
LaRue, J. M., Stratagoules, E. D., & Martinez, J. D. (2000). Cancer Letters, 152(1), 107–113.
Yui, S., Saeki, T., Kanamoto, R., & Iwami, K. (2005). Journal of biochemistry, 138(2), 151–157.
Perez, M. J., & Briz, O. (2009). World journal of gastroenterology, 15(14), 1677.
Payne, C. M., Crowley-Skillicorn, C., Bernstein, C., Holubec, H., Moyer, M. P., & Bernstein, H. (2010). Nutrition and cancer, 62(6), 825–840.
Song, W., Shen, D. Y., Kang, J. H., Li, S. S., Zhan, H. W., Shi, Y., et al. (2012). World Journal of Gastroenterology, 18(7), 704–711.
Simon, H.-U., Haj-Yehia, A., & Levi-Schaffer, F. (2000). Apoptosis, 5(5), 415–418.
Qin, F., Song, Y., Li, Z., Zhao, L., Zhang, Y., & Geng, L. (2010). Pathology & Oncology Research, 16(3), 353–360.
Kim, Y. H., Shin, K. J., Lee, T. G., Kim, E., Lee, M. S., Ryu, S. H., et al. (2005). Biochemical Pharmacology, 69(9), 1333–1341.
Hunot, S., & Flavell, R. A. (2001). Science, 292(5518), 865–866.
Kang, J. H., Zhang, W. Q., Song, W., Shen, D. Y., Li, S. S., Tian, L., et al. (2012). Applied Biochemistry and Biotechnology, 166(4), 942–951.
Milovic, V., Teller, I. C., Faust, D., Caspary, W. F., & Stein, J. (2002). European Journal Clinical Investigation, 32(1), 29–34.
Zhang, H.-T., Luo, H., Wu, J., Lan, L.-B., Fan, D.-H., Zhu, K.-D., et al. (2010). World Journal of Gastroenterology, 16(27), 3377.
Im, E., Choi, S.-H., Suh, H., Choi, Y. H., Yoo, Y. H., & Kim, N. D. (2005). Cancer Letters, 229(1), 49–57.
Hock, A. K., & Vousden, K. H. (2012). Cell, 149(6), 1183–1185.
Li, T., Kon, N., Jiang, L., Tan, M., Ludwig, T., Zhao, Y., et al. (2012). Cell, 149(6), 1269–1283.
Lowe, S. W., & Lin, A. W. (2000). Carcinogenesis, 21(3), 485–495.
Acknowledgments
The present investigation was supported by grant from the Natural Science Foundation of China (30871241).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Song, W., Yang, HB., Chen, P. et al. Apoptosis of Human Gastric Carcinoma SGC-7901 Induced by Deoxycholic Acid via the Mitochondrial-Dependent Pathway. Appl Biochem Biotechnol 171, 1061–1071 (2013). https://doi.org/10.1007/s12010-013-0417-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12010-013-0417-6