Depleting Glycine and Sarcosine in Prostate Cancer Cells as a New Treatment for Advanced Prostate Cancer.

摘要

Glycine is consumed b y rapidly proliferating cancer cells but not rapidly proliferating normal cells, which offers an opportunity to deplete glycine and inhibit cancer cells without affecting normal cells. The major source of intracellular glycine is a reversible conversion of serine through serine hydroxymethyltransferases (SHMT). Glycine is required for synthesis of purines, proteins, glutathione, and sarcosine. Sarcosine is associated with invasion, migration, and metastasis of prostate cancer. Aminomethylphosphonic acid (AMPA) is an analog of glycine that can inhibit SHMT s enzyme activities, thus being able to block conversion of serine into glycine and subsequently to decrease sarcosine. We hypothesize that AMPA may inhibit proliferation, invasion, migration, and metastasis of prostate cancer through depleting glycine and sarcosine. In the one - year performance period, we found that AMPA indeed inhibited proliferation, invasion, migration, and metastasis of prostate cancer in the in vitro and in vivo experiment