CATIONIC PEPTIDE LACTOFERRICIN B INHIBITS GLUTATHIONE S-TRANSFERASE P1 FROM HUMAN PLACENTA AND BREAST CANCER CELL LINE MDA-MB-231 PREVENTING ANTICANCER DRUG METABOLISM
Journal Title: International Journal of Pharmacy and Pharmaceutical Sciences - Year 2015, Vol 7, Issue 8
Abstract
Objective: To investigate the interaction of LfcinB (Lactoferricin B) with GSTP1 (Glutathione S-Transferase P1) from human placental and breast cancer cell line MDA-MB-231.Methods: We examined the interaction of Lfcin B with human placental GSTP1 and breast adenocarcinoma MD-MB-231 cell line. Enzyme activity of GSTP1 was measured with and without pre-incubation with Lfcin B. Kinetic variables were determined by incubating the enzyme reaction mixture with fixed GSH (reduced glutathione) concentration and varying CDNB (1-chloro-2, 4-dinitrobenzene) concentrations or fixed CDNB concentration and varying GSH concentrations.Results: Lfcin B is a competitive inhibitor with respect to GSH binding site (G site) and noncompetitive inhibitor with respect to hydrophobic substrate unit (H site) of human placental GSTP1 enzyme. Lfcin B was also incubated with GSTP1 from breast adenocarcinoma MDA-MB-231 cell line. The activity of GSTP1 was much higher (0.2665 μ mol/ml/min) in Lfcin B untreated MDA-MB-231 cell line, whereas MDA-MB-231 with Lfcin B treatment showed a very low activity (0.0254 μ mol/ml/min).Conclusion: Our Findings suggest that Lfcin B can inhibit the GSTP1 activity in human placental and MDA-MB-231 breast cancer cell lines, which may induce synergistic effects when used in combination with antineoplastic drugs that are substrates of GSTP1 enzyme. This combination will exert a double attack on cancers over expressing GSTP1, first sensitizing them to anticancer drugs by preventing their metabolism.Â
Authors and Affiliations
Amir Riyaz Khan, Pankaj Taneja
Keywords
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