Bacteriophages M13 and T4 Increase the Expression of Anchorage-Dependent Survival Pathway Genes and Down Regulate Androgen Receptor Expression in LNCaP Prostate Cell Line.

Swapnil Ganesh Sanmukh,Márcio De Carvalho,Nilton José Dos Santos,Maira Smaniotto Cucielo,Caroline Nascimento Barquilha,Patricia Pintor Dos Reis,Hernandes F Carvalho,Sérgio Luis Felisbino,Flávia Karina Delella

doi:10.3390/v13091754

Swapnil Ganesh Sanmukh, Márcio De Carvalho + Show 7 more

Open Access

https://doi.org/10.3390/v13091754

Copy DOI

Abstract

Wild-type or engineered bacteriophages have been reported as therapeutic agents in the treatment of several types of diseases, including cancer. They might be used either as naked phages or as carriers of antitumor molecules. Here, we evaluate the role of bacteriophages M13 and T4 in modulating the expression of genes related to cell adhesion, growth, and survival in the androgen-responsive LNCaP prostatic adenocarcinoma-derived epithelial cell line. LNCaP cells were exposed to either bacteriophage M13 or T4 at a concentration of 1 × 105 pfu/mL, 1 × 106 pfu/mL, and 1 × 107 pfu/mL for 24, 48, and 72 h. After exposure, cells were processed for general morphology, cell viability assay, and gene expression analyses. Neither M13 nor T4 exposure altered cellular morphology, but both decreased the MTT reduction capacity of LNCaP cells at different times of treatment. In addition, genes AKT, ITGA5, ITGB1, ITGB3, ITGB5, MAPK3, and PI3K were significantly up-regulated, whilst the genes AR, HSPB1, ITGAV, and PGC1A were down-regulated. Our results show that bacteriophage M13 and T4 interact with LNCaP cells and effectively promote gene expression changes related to anchorage-dependent survival and androgen signaling. In conclusion, phage therapy may increase the response of PCa treatment with PI3K/AKT pathway inhibitors.

Highlights

Prostate Cancer (PCa) is the second leading cause of death in men globally [1,2]
LNCaP cells exposed to bacteriophages M13 and T4 at 1 × 107 pfu/mL showed no significant morphological alterations after 24 h, as compared to untreated cells (Figure 1)
The exposure to bacteriophages temporarily reduced the viability of prostate cancer cells

Summary

Introduction

Prostate Cancer (PCa) is the second leading cause of death in men globally [1,2]. PCa is curable in most cases if detected before causing distant metastasis to bone and other body organs [3,4]. Phage-based therapies, as well as phage lytic-enzyme therapies, have been reported. The effects of phages on cancer cells in vitro as well as in vivo are promising [8,9,10,11,12]. Hybrid phages or modified phages have been developed by various groups worldwide to detect, target, and attack different cancer cells including PCa [10,13,14,15]

Methods

Results

Discussion

Conclusion