Sunil Sagar, Luke Esau, Mandeep kaur, Vladimir B. Bajic

 
Computational Bioscience Research Center, King Abdullah University of Science and Technology (KAUST), Saudia Arabia

Abstract:

Plumbagin [5-hydroxy- 2-methyl-1, 4-naphthaquinone] is a well-known plant derived anti-cancer lead compound. Several efforts have been made to synthesize its analogs and derivatives, to further increase its anti-cancer potential. In the present study, five derivatives of plumbagin i.e. A, B, C, D, and E were synthesized and evaluated for their anti-proliferative activity. Pre-screening against four human cancer and one normal cell line through MTT assay at various time points lead us to choose A (Acetyl plumbagin) for further investigations in MCF-7 (estrogen receptor positive) and BT20 (estrogen receptor negative), along with normal fibroblasts (BJ) through various assays: APOPercentage assay, caspase-3/7 assay, cell cycle analysis and investigation of apoptosis-associated genes such as p53, Mdm2, NF-kB, Bad, Bax, Bcl-2 and Casp-7 using RT-PCR. The results suggest that Derivative A has selective apoptotic activity similar to plumbagin against breast cancer MCF-7 cells; however, contrary to plumbagin behavior, normal fibroblasts were relatively unaffected. Derivative A also displayed negligible hepatotoxicity towards HepG2 cell line. Overall results showed that derivative A has the potential to be a new lead molecule for testing against estrogen positive breast cancer.

Keywords: Anticancer, Plumbagin, Apoptosis.