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ABSTRACT Targeting tumor metabolism offers a promising therapeutic avenue for colon cancer. Our study demonstrated that apigenin (Api), a natural flavonoid, exerted antitumor effects against colon cancer both in vitro and in vivo with minimal toxicity. Multi‐omics profiling revealed that Api coordinately disrupted central carbon metabolism and proliferation‐related pathways. Mechanistically, Api treatment in HCT‐116 cells suppressed the expression of pyruvate kinase M2 (PKM2), markedly inhibited lactate production, decreased adenosine triphosphate (ATP) generation rates from both glycolysis and oxidative phosphorylation, and dissipated mitochondrial membrane potential, collectively inducing a profound bioenergetic crisis. This metabolic collapse was accompanied by robust apoptosis, evidenced by increased apoptotic cells and cleavage of PARP‑1 and caspase‑3. Crucially, PKM2 overexpression attenuated Api‐induced metabolic suppression, cytotoxicity, and apoptotic marker accumulation, establishing PKM2 as a key functional target. Our findings establish PKM2 as a key functional target in Api‐induced energy crisis and apoptosis, underscoring its potential as a low‐toxicity therapy for colon cancer.
Zhang et al. (Thu,) studied this question.