The Triple Combination of Recombinant Methioninase, Rapamycin, and Chloroquine Synergistically Eradicates HCT116 Colon Cancer Cells

Abstract

Background/aim: The prognosis for advanced/metastatic colon cancer is poor, with low survival rates despite aggressive treatment. Recombinant methioninase (rMETase) targets the methionine addiction of cancer and works synergistically with many anticancer drugs. The present study aimed to determine the synergistic efficacy of the combination of rMETase, rapamycin (RAPA), and chloroquine (CQ) on human HCT116 colon cancer cells in vitro.

Materials and methods: The half-maximal inhibitory concentrations (IC₅₀) of rMETase, RAPA, and CQ were determined for the human HCT116 cell line in vitro. The synergy of rMETase combined with RAPA; rMETase combined with CQ; and rMETase combined with RAPA and CQ, at their respective IC₅₀ values, was determined on HCT116 cells. Cell viability was measured with the WST-8 reagent.

Results: The IC₅₀ value of rMETase was 0.48 U/ml; for RAPA 19.6 μM; and for CQ 16.5 μM on the HCT116 cell line. Synergy was observed with both the combination of rMETase and RAPA (p=0.02) and the combination of rMETase and CQ (p=0.03). The triple combination of rMETase, RAPA, plus CQ showed the strongest synergistic efficacy, eradicating HCT116 cells (p=0.01).

Conclusion: The triple combination of rMETase, RAPA and CQ shows strong synergistic efficacy on the human HCT116 colon cancer cell line. The results of the present study suggest the potential for future clinical applications of this triple-combination treatment for advanced/metastatic colon cancer.

Keywords: HCT116 cells; Hoffman effect; Methioninase; chloroquine; colon cancer; methionine addiction; rapamycin; synergy.