Salmonella typhimurium A1-R and Cell-Cycle Decoy Therapy of Cancer

Abstract

Cancer cells in G0/G1 are resistant to cytotoxic chemotherapy agents which kill only cycling cancer cells. Salmonella typhimurium A1-R (S. typhimurium A1-R) decoyed cancer cells in monolayer culture and in tumor spheres to cycle from G0/G1 to S/G2/M, as demonstrated by fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging. S. typhimurium A1-R targeted FUCCI-expressing subcutaneous tumors, and tumors growing on the liver, growing in nude mice and also decoyed quiescent cancer cells, which were the majority of the cells in the tumors, to cycle from G0/G1 to S/G2/M. The S. typhimurium A1-R-decoyed cancer cells became sensitive to cytotoxic agents.

Keywords: Amino acid; Auxotroph; Cancer; Cell cycle; Chemotherapy; Decoy; Fluorescence ubiquitination-based cell cycle indicator (FUCCI); Green fluorescent protein (GFP)Red fluorescent protein (RFP); Imaging; Metastasis; Mouse models; Nude mice; Salmonella typhimurium A1-R; Surgical orthotopic implantation (SOI); Tumor-targeting.