PLUMBAGIN DERIVATIVE AS A POTENTIAL LEAD MOLECULE FOR ESTROGEN
POSITIVE BREAST CANCER
Sunil Sagar, Luke Esau, Mandeep kaur, Vladimir B. Bajic
Computational Bioscience Research Center, King Abdullah University of Science and Technology (KAUST), Saudia Arabia
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.