Journal of Hematology & Thromboembolic Diseases
Open Access

Abstract

An Innovative Cis-Diammineplatinum (II) Benzene-Polycarboxylic-Acids Complex Inhibits Growth of Burkitt`s Cell Lymphoma In Vitro and In Vivo

Steen Lindkær-Jensen, Claus L. Jensen, Naiel Azzam, Rinat Bar-Shalom, Basem Fares, Nina Habib L Jensen, Stig Larsen and Fuad Fares

Cis-diammineplatinum (II) benzene-polycarboxylic acids (CDBPA) is a new therapy of solid tumors without toxicity, mild and transient side-effects and an ability to improve quality of life. The underlying mechanism of action of CDBPA in Burkitt`s lymphoma was tested in vitro and its effect on tumor size and survival was tested in a NOD-scid mice model. BL cells and normal fibroblasts were exposed to CDBPA for cytotoxicity screening by XTT assay, followed by cell cycle arrest, determination of apoptosis using Flow Cytometry and by annexin V/FITC/PI assay. Protein level and Gene expression were tested by Western blotting analysis and by the Applied Biosystems� Tagman� Array Plates, respectively. We demonstrated that CDBPA significantly reduced cell viability and induced apoptosis via the extrinsic and the intrinsic apoptotic pathways of Burkitts lymphoma cells without causing cell cycle arrest but reduction of the various phases. Gene expression experiments indicated that CARD9, BNIP3(L), TNFRSF-1B, and TNFRSF-25 genes are highly expressed in Ramos BL cells following treatment with CDBPA. CDBPA exerted a strong apoptotic cell death. A gene expression profile analysis has been performed and the results indicated that CBPDA is significantly increased the expression of five genes: CARD9, BNIP, TNFRSF-1B, TNFRSF25 and TNF-alpha, that have an important role in induction of apoptosis. This means that apoptosis is induced by NF?B in two ways. The survival period of mice treated with subcutaneous CDBPA was longer than that of mice treated with vehicle or R-CHOP. Tumor size was significantly reduced after 2 weeks of treatment with CDBPA. CDBPA, possesses strong in vitro and in vivo activity against Ramos cells, representing a potential approach for therapy of Burkitt lymphoma.