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Butein (3,4,2',4'-tetrahydroxychalcone) is a polyphenol derived from various natural plants and is capable of inducing several types of death in cancer cells. However, the molecular mechanisms underlying butein-induced breast cancer cell apoptosis remain unknown. The present study aimed to prove that butein inhibits the proliferation of MDA-MB‑231 human breast cancer cells in a dose- and time-dependent manner. Butein markedly induced the generation of reactive oxygen species (ROS), decreased the phosphorylation of extracellular signal-regulated kinase (ERK), increased p38 activity, diminished Bcl-2 expression, induced caspase 3 cleavage and was associated with poly(ADP-ribose) polymerase (PARP) cleavage. Our findings also indicate that ROS may play an important role in butein-induced apoptosis, as pre-treatment with the antioxidant, N-acetyl cysteine (NAC), prevented butein-induced apoptosis. In conclusion, our results demonstrate that butein inhibits the proliferation of breast cancer cells through the generation of ROS and the modulation of ERK and p38 activities. We also demonstrate that these effects may be abrogaged by pre-treatment with NAC. Our results suggest that butein may function as a potential therapeutic agent for the treatment of breast cancer.

Flavonoids exhibit chemopreventive and chemotherapeutic effects. Butein, a bioactive flavonoid isolated from numerous native plants, has been shown to induce apoptosis in human cancer cells. In the current study, the molecular mechanisms of butein action on cell proliferation and apoptosis of neuroblastoma cells were evaluated. Treatment with butein decreased the viability of Neuro-2A neuroblastoma cells in a dose- and time-dependent manner. The dose-dependent nature of butein-induced apoptosis was characterized by an increase in the sub-G1 phase population. Treatment with butein significantly increased intracellular reactive oxygen species (ROS)levels and reduced the Bcl-2/Bax ratio, triggering the cleavage of pro-caspase 3 and poly-(ADP-ribose) polymerase (PARP). Pre-treatment with the antioxidant agent, N-acetyl cysteine (NAC), blocks butein-induced ROS generation and cell death. NAC also recovers butein-induced apoptosis-related protein alteration. In conclusion, butein-triggered neuroblastoma cells undergo apoptosis via generation of ROS, alteration of the Bcl‑2/Bax ratio, and cleavage of pro-caspase 3 and PARP. Our results suggest that butein may serve as a potential therapeutic agent for the treatment of neuroblastoma.