Combination of Recombinant Methioninase With Rapamycin or Chloroquine Is Synergistic to Highly Inhibit Triple-negative Breast Cancer Cells In Vitro.

Background/aim: Triple-negative breast cancer (TNBC) is a highly aggressive and heterogeneous subtype of breast cancer with a poor prognosis despite multimodal treatment. New therapeutic approaches for TNBC are necessary. We very recently showed that the triple combination of recombinant methioninase (rMETase), rapamycin (RAPA), and chloroquine (CQ) synergically eradicated osteosarcoma cells in vitro. The present study aimed to determine whether rMETase has synergistic efficacy with either RAPA or CQ on a TNBC cell line.

Materials and methods: The half-maximal inhibitory concentrations (IC₅₀) of rMETase, RAPA, and CQ were determined on the human MDA-MB-231 TNBC cell line in vitro. The efficacy of rMETase, combined with RAPA or with CQ, at their respective IC₅₀ values, on MDA-MB-231 cell viability was determined using the WST-8 assay.

Results: The IC₅₀ of rMETase was 0.56 U/ml, for RAPA the IC₅₀ was 3.9 μM, and for CQ the IC₅₀ was 5.0 μM. The viability of the MDA-MB-231 cells was significantly decreased after treatment with rMETase plus RAPA or rMETase plus CQ, compared to the control cells or cells treated with one drug only.

Conclusion: rMETase, when combined with either RAPA or CQ, is synergistic on the MDA-MB-231 TNBC cell line. The present findings suggest the potential for future clinical applications of rMETase plus chemotherapy, such as RAPA or CQ, for recalcitrant TNBC.