Nano-gossypin, a novel cdk2/VEGF inhibitor formulation against breast cancer.

Abstract

Abstract Abstract #3080 Cyclin-dependent kinases (CDKs) play essential roles in the intracellular control of the cell cycle. The encapsulated therapeutic drug molecules as nanoparticles will offer a sustained delivery of chemotherapeutics in to the target tissue. Nanoparticles enhance the therapeutic efficacy of an encapsulated drug by increased and sustained delivery of the drug inside the cell. Most anticancer drugs are taken up non-specifically by all types of cells, resulting in serious side-effects. Therefore, an ideal delivery carrier for an anticancer drug should be able to transport the drug specifically to cancer cells and release the drug molecules inside the cells to the site of their pharmacological activities. Most of the activity proven natural products were not entered in to the clinical practice due to lack of active formulation and/ or effective targeted delivery systems. In our study we found that gossypin (3,5,7,3',4'-Pentahydroxy-8-O-glucosylflavone) is inhibiting cell cycle progression by inhibiting cyclin dependent kinase-2 (cdk2) when compared with roscovitine, a known cdk2 inhibitor. Gossypin has been shown to induce the accumulation of the tumor suppressor p53, cell cycle arrest in G1 and G2/M phases of the cell cycle, and to induce apoptosis in MCF-7, SKBR-3, and MDA-MB-231 cells with a mean IC 50 of 40uM. Gossypin also found to inhibit vascular endothelial growth factor (VEGF) in vitro. Nanoparticle formulation of gossypin effectively inhibited the growth and colony formation in vitro when compared to parent compound. Gossypin might exert inhibition of tumor cell growth and invasion by cell cycle arrest as well as VEGF induced vascular permeability and tumor neovascularization. The dual mode of action of gossypin may results in highly efficacious inhibition of tumor growth and management of breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3080.