CATIONIC PEPTIDE LACTOFERRICIN B INHIBITS GLUTATHIONE S-TRANSFERASE P1 FROM HUMAN PLACENTA AND BREAST CANCER CELL LINE MDA-MB-231 PREVENTING ANTICANCER DRUG METABOLISM

  • Amir Riyaz Khan Department of Biotechnology, School of Engineering and Technology, Sharda University, Knowledge Park-III, Gautam Buddha Nagar, Greater Noida, Uttar Pradesh, Pin code-201306, India
  • Pankaj Taneja Adjunct Scientist, Wake Forest School of Medicine, Winston Salem, NC 27103, USA

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.

 

Keywords: Cationic peptide, Lactoferricin B, Glutathione S Transferase P1, Enzyme activity, Inhibitor

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Author Biographies

Amir Riyaz Khan, Department of Biotechnology, School of Engineering and Technology, Sharda University, Knowledge Park-III, Gautam Buddha Nagar, Greater Noida, Uttar Pradesh, Pin code-201306, India

PhD Researh Fellow ( Cancer Therapeutics)

 

Pankaj Taneja, Adjunct Scientist, Wake Forest School of Medicine, Winston Salem, NC 27103, USA
Adjunct Scientist, Wake Forest School of Medicine, Winston Salem, NC 27103, USA

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Khan, A. R., and P. Taneja. “CATIONIC PEPTIDE LACTOFERRICIN B INHIBITS GLUTATHIONE S-TRANSFERASE P1 FROM HUMAN PLACENTA AND BREAST CANCER CELL LINE MDA-MB-231 PREVENTING ANTICANCER DRUG METABOLISM”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 8, June 2015, pp. 238-41, https://innovareacademics.in/journals/index.php/ijpps/article/view/7189.
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