Glycine decarboxylase (GLDC) is a very recently identified metabolic oncogene that links glycine metabolism with tumorigenesis. We designed this study to determine the mechanistic role of GLDC in in ovarian cancer cells. First, we confirmed the expressions of GLDC in eight different ovarian cancer cell lines. And colony formation assay revealed decreased proliferation of OVCAR3 ovarian cancer cells transfected with siGLDC compared with that of control. Intriguingly, we found that knockdown of GLDC induced decreased S-adenosylmethionine (SAM)/ S-adenosylhomocysteine (SAH) ratio, which implicates methyl donor deficient state in OVCAR3 cells. Expressions of sirtuin 1 (SIRT1), heat shock protein (HSP) 90 and heat-shock factor protein 1 (HSF1) decreased while that of p53 increased in GLDC knock-downed cells, suggesting heat shock response. Addition of SAM into siGLDC knock-downed cell restored the expression of SIRT1. Inhibition of SIRT1 decreased Bcl2 and increased cytochrome c expressions. In summary, these results suggest GLDC induces methyl donor deficient state in OVCAR3 ovarian cancer cells, which in turn leads to apoptosis via SIRT1-mediated pathway.

Citation Format: So-Jin Shin, Jin-Young Kim, Eun-Young Ha, Chi-Heum Cho. Glycine decarboxylase inhibits proliferation of ovarian cancer cells via SIRT1-mediated apoptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4459. doi:10.1158/1538-7445.AM2017-4459

©2017 American Association for Cancer Research.
2017
American Association for Cancer Research.