DTMP imbalance through thymidylate 5'-phosphohydrolase activity induces apoptosis in triple-negative breast cancers.

ABSTRACT: Immunotherapy has a number of advantages over traditional anti-tumor therapy but can cause severe adverse reactions due to an overactive immune system. In contrast, a novel metabolic treatment approach can induce metabolic vulnerability through multiple cancer cell targets. Here, we show a therapeutic effect by inducing nucleotide imbalance and apoptosis in triple negative breast cancer cells (TNBC), by treating with cytosolic thymidylate 5'-phosphohydrolase (CT). We show that a sustained consumption of dTMP by CT could induce dNTP imbalance, leading to apoptosis as tricarboxylic acid cycle intermediates were depleted to mitigate this imbalance. These cytotoxic effects appeared to be different, depending on substrate specificity of the 5' nucleotide or metabolic dependency of the cancer ce

SUBMITTER: Kim DH 

PROVIDER: S-EPMC9681768 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature