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

Area of Science:

• Oncology
• Microbiology
• Cell Biology

Background:

• Cancer cells in the G0/G1 phase of the cell cycle are resistant to conventional chemotherapy.
• Cytotoxic chemotherapy agents are effective primarily against rapidly dividing cancer cells.
• Quiescent cancer cells represent a significant population within tumors, contributing to treatment resistance.

Purpose of the Study:

• To investigate the effect of Salmonella typhimurium A1-R (S. typhimurium A1-R) on the cell cycle status of cancer cells.
• To determine if S. typhimurium A1-R can induce quiescent cancer cells to enter the cell cycle.
• To assess the impact of S. typhimurium A1-R-induced cell cycle progression on cancer cell sensitivity to chemotherapy.

Main Methods:

• Utilized fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging to monitor cancer cell cycle progression.
• Administered S. typhimurium A1-R to cancer cells in monolayer cultures and tumor spheres.
• Inoculated nude mice with FUCCI-expressing tumors (subcutaneous and liver) and treated with S. typhimurium A1-R.

Main Results:

• S. typhimurium A1-R successfully decoyed cancer cells in vitro and in vivo to cycle from G0/G1 to S/G2/M phases.
• The majority of cancer cells within tumors, including quiescent cells, were induced to re-enter the cell cycle by S. typhimurium A1-R.
• Cancer cells decoyed into cycling by S. typhimurium A1-R demonstrated increased sensitivity to cytotoxic chemotherapy agents.

Conclusions:

• S. typhimurium A1-R effectively targets and stimulates quiescent cancer cells to re-enter the cell cycle.
• This cell cycle re-entry mediated by S. typhimurium A1-R renders previously resistant cancer cells vulnerable to chemotherapy.
• S. typhimurium A1-R holds potential as a therapeutic agent to overcome chemotherapy resistance in cancer treatment.