Phosphaplatins Are Potent Inducers Of Pigment Epithelial- Derived Factor (Pedf)

Pigment Epithelial Derived Factor (PEDF) is a secreted glycoprotein that exhibits several biological activities, most notably as a potent anti-angiogenic agent as well as a neurotrophic factor. As such, this molecule has potential application as therapeutics for cancer and a variety of neurological diseases. However, prior art methods directed towards enhancing and stabilizing PEDF expression in vivo have met with little success. Therefore, methods that could lead to the stable expression of PEDF in vivo are still needed. We have recently shown that PEDF protein is overexpressed in tumor cells treated with platinum based drugs; phosphaplatins that are platinum-(II) and platinum-(IV) complexes coordinated to a pyrophosphate moiety. The objective of this study is to extend our previous findings by measuring PEDF expression in both malignant cells and normal neuronal tissues after treating them with these compounds. We also investigated the impact of PEDF upregulation on important biological processes such as apoptosis, proliferation and invasion of tumor cells. Our data showed that there was a significant upregulation (over 4-fold) of PEDF in brain of mice treated with phosphoplatins when compared to the control animals. The compounds were found to stimulate PEDF expression in cultured neuronal cells when assessed in vitro (P Citation Format: Louiza Belkacemi, Armando Rivera, Lu Yang, Rathindra N. Bose, Shaun X. Zhang. Phosphaplatins are potent inducers of pigment epithelial- derived factor (PEDF). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3806.