Oncotarget

Research Papers:

Anti-proliferative role of recombinant lethal toxin of Bacillus anthracis on primary mammary ductal carcinoma cells revealing its therapeutic potential

Rekha Khandia, Bramhadev Pattnaik, Katherukamem Rajukumar, Atul Pateriya, Sandeep Bhatia, Harshad Murugkar, Anil Prakash, Hare Krishna Pradhan, Kuldeep Dhama, Ashok Munjal and Sunil K. Joshi _

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Oncotarget. 2017; 8:35835-35847. https://doi.org/10.18632/oncotarget.16214

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Abstract

Rekha Khandia1,6, Bramhadev Pattnaik2, Katherukamem Rajukumar1, Atul Pateriya1, Sandeep Bhatia1, Harshad Murugkar1, Anil Prakash3, Hare Krishna Pradhan4, Kuldeep Dhama5, Ashok Munjal6, Sunil K. Joshi7

1ICAR-National Institute of High Security Animal Diseases, Bhopal, Madhya Pradesh, India

2Project Directorate on Foot and Mouth Disease, Mukteswar, Uttarakhand, India

3Department of Microbiology, Barkatullah University, Bhopal, Madhya Pradesh, India

4Ex-Avian Influenza National Consultant, Indian Office of WHO Consultant, Bhartiya Kala Kendra, New Delhi, India

5Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly Uttar Pradesh, India

6Department of Biochemistry and Genetics, Barkatullah University, Bhopal, Madhya Pradesh, India

7Cellular Immunology Laboratory, Frank Reidy Research Center of Bioelectrics, College of Health Sciences, Old Dominion University, Norfolk, VA USA

Correspondence to:

Sunil K. Joshi, email: skjoshi@odu.edu

Ashok Munjal, email: ashokmunjal70@yahoo.co.in

Keywords: anthrax toxin receptor, bacillus anthracis, c-Met receptor, lethal factor, protective antigen

Received: January 02, 2017     Accepted: March 07, 2017     Published: March 15, 2017

ABSTRACT

Bacillus anthracis secretes three secretary proteins; lethal factor (LF), protective antigen (PA) and edema factor (EF). The LF has ability to check proliferation of mammary tumors, chiefly depending on mitogen activated protein kinase (MAPK) signaling pathway. Evaluation of therapeutic potential of recombinant LF (rLF), recombinant PA (rPA) and lethal toxin (rLF + rPA = LeTx) on the primary mammary ductal carcinoma cells revealed significant (p < 0.01) reduction in proliferation of tumor cells with mean inhibition indices of 28.0 ± 1.37% and 19.6 ± 1.47% respectively. However, treatment with rPA alone had no significant anti-proliferative effect as evident by low mean inhibition index of 3.4 ± 3.87%. The higher inhibition index observed for rLF alone as compared to LeTx is contrary to the existing knowledge on LF, which explains the requirement of PA dependent endocytosis for its enzymatic activity. Therefore, the plausible existence of PA independent mode of action of LF including direct receptor mediated endocytosis or modulation of signal transduction cascade via unknown means is hypothesized. In silico protein docking analysis of other cellular receptors for any plausibility to play the role of receptor for LF revealed c-Met receptor showing strongest affinity for LF (H bond = 19; Free energy = −773.96), followed by nerve growth factor receptor (NGFR) and human epidermal growth factor receptor (HER)-1. The study summarizes the use of rLF or LeTx as therapeutic molecule against primary mammary ductal carcinoma cells and also the c-Met as potential alternative receptor for LF to mediate and modulate PA independent signal transduction.


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