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Combination of Recombinant Methioninase With Rapamycin or Chloroquine Is Synergistic to Highly Inhibit

Jinsoo Kim1,2,3, Qinghong Han1, Byung Mo Kang1,2

  • 1AntiCancer Inc., San Diego, CA, U.S.A.

Anticancer Research
|April 28, 2025
PubMed
Abstract

Insights

Recombinant methioninase (rMETase) combined with rapamycin (RAPA) or chloroquine (CQ) shows synergistic effects against triple-negative breast cancer (TNBC) cells, suggesting potential new treatments for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Triple-negative breast cancer (TNBC) is an aggressive cancer subtype with limited treatment options.
  • Novel therapeutic strategies are urgently needed for TNBC.
  • Previous research indicated synergistic effects of recombinant methioninase (rMETase), rapamycin (RAPA), and chloroquine (CQ) on osteosarcoma cells.

Purpose of the Study:

  • To investigate the synergistic efficacy of rMETase in combination with RAPA or CQ on a TNBC cell line.
  • To evaluate the potential of these drug combinations as a new therapeutic approach for TNBC.

Main Methods:

  • Determined the half-maximal inhibitory concentrations (IC50) for rMETase, RAPA, and CQ on the MDA-MB-231 TNBC cell line in vitro.
  • Assessed the impact of combined rMETase with RAPA or CQ at their IC50 values on MDA-MB-231 cell viability using the WST-8 assay.

Main Results:

  • The IC50 values were established as 0.56 U/ml for rMETase, 3.9 μM for RAPA, and 5.0 μM for CQ.
  • Combined treatment with rMETase plus RAPA or rMETase plus CQ significantly reduced MDA-MB-231 cell viability compared to single-drug treatments or controls.

Conclusions:

  • rMETase exhibits synergistic effects when combined with either RAPA or CQ on the MDA-MB-231 TNBC cell line.
  • These findings support the potential clinical application of rMETase in combination with chemotherapy agents like RAPA or CQ for treating difficult TNBC.
  • Further research is warranted to explore these combinations in clinical settings.
Keywords:
Hoffman effectMDA-MB-231 cellsMethionine addictionchloroquinecombinationmethioninaserapamycinsynergytriple-negative breast cancer

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