Efficacy of Methionine Restriction and the PARP-inhibitor Olaparib and Their Combination on Mutant and Wild-type Triple-negative Breast Cancer Cell Lines.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is a recalcitrant disease. The present study examined the efficacy of methionine restriction and the poly ADP-ribose polymerase (PARP)-inhibitor olaparib on wild-type and mutated TNBC cell lines.

MATERIALS AND METHODS

The human wild-type cell line MDA-MB-231, and -mutant cell lines MDA-MB-436 and HCC1937 were used to examine sensitivity to recombinant methioninase (rMETase) or a methionine-free medium or to olaparib or the combination of a methionine-free medium and olaparib. Cell viability was examined using the WST-8 reagent as well as by direct cell counting after Hoechst 33342 staining.

RESULTS

MDA-MB-231 was sensitive to a methionine-free medium and rMETase and resistant to olaparib. The combination of olaparib and a methionine-free medium was not synergistic on MDA-MB-231 cells. MDA-MB-436 cells were not sensitive to a methionine-free medium but were sensitive to olaparib and rMETase. The combination of olaparib and a methionine medium was not synergistic in MDA-MB-436 cells. HCC1937 cells were sensitive to a methionine-free medium, partially sensitive to rMETase, partially resistant to olaparib, and sensitive to the combination of a methionine-free medium and olaparib. All three cell lines were sensitive to rMETase, with MDA-MB-436 being the most sensitive.

CONCLUSION

Methionine restriction and olaparib showed synergistic efficacy on the -mutant TNBC cell line HCC1937. The BRCA1-mutant cell line MDA-MB-436 was most sensitive to rMETase. The wild-type TNBC cell line MDA-MB-231 was sensitive to a methionine-free medium but resistant to olaparib. Therefore, methionine restriction has clinical potential for wild-type and -mutant olaparib-resistant and -sensitive TNBC.