Genistein–Butein Co-Treatment Suppresses Glycolytic Metabolism and Induces Apoptotic Signaling in PC-3 Prostate Cancer Cells

TL;DR

Combining genistein and butein reduces prostate cancer cell viability by disrupting energy metabolism and triggering cell death.

Contribution

This study reveals the combined effect of genistein and butein on suppressing glycolysis and inducing apoptosis in PC-3 prostate cancer cells.

Findings

GEN/BTN co-treatment reduced PC-3 cell viability more effectively than either compound alone.

The combination suppressed glycolytic metabolism and depleted ATP levels in cancer cells.

Apoptotic signaling was activated through caspase-3 and PARP cleavage, with reduced AKT and ERK phosphorylation.

Abstract

Prostate cancer progression involves metabolic reprogramming that supports sustained proliferation and survival, highlighting metabolic pathways as potential targets for intervention. While genistein (GEN) and butein (BTN) are naturally occurring polyphenolic compounds with reported anticancer activities, their combined effects on prostate cancer cell metabolism and apoptotic signaling remain unclear. Here, we investigated the effects of GEN and BTN, administered individually and in combination, on human PC-3 prostate cancer cells, with normal human prostate epithelial cells (HPrEC) used for comparison. Cell viability was assessed using MTT and trypan blue exclusion assays. Glycolytic metabolism was evaluated by measuring glucose consumption, lactate production, hexokinase and pyruvate dehydrogenase activity, and intracellular ATP levels, while apoptotic and survival signaling pathways were analyzed by means of Annexin V staining and Western blotting. GEN/BTN co-treatment selectively reduced PC-3 cell viability, producing greater inhibitory effects than either compound alone. This enhanced response was accompanied by suppression of glycolytic metabolism, ATP depletion, attenuation of AKT and ERK phosphorylation, and activation of apoptotic signaling, as evidenced by increased cleavage of caspase-3 and PARP. Collectively, these findings indicate that GEN/BTN co-treatment cooperatively disrupts glycolytic metabolism while activating apoptotic signaling in prostate cancer cells.

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