Cardamonin induces G2/M arrest and apoptosis via activation of the JNK-FOXO3a pathway in breast cancer cells
Abstract
Cardamonin (CD), a naturally occurring chalcone isolated from large black cardamom, was previously reported to suppress the proliferation of breast cancer cells. However, its precise molecular anti-tumor mechanisms have not been well elucidated. In this study, we found that CD markedly inhibited the proliferation of MDA-MB 231 and MCF-7 breast cancer cells through the induction of G2/M arrest and apoptosis. Reactive oxygen species (ROS) plays a pivotal role in the inhibition of CD-induced cell proliferation. Treatment with N-acetyl-cysteine (NAC), an ROS scavenger, blocked CD-induced G2/M arrest and apoptosis in this study. Quenching of ROS by overexpression of catalase also blocked CD-induced cell cycle arrest and apoptosis. We showed that CD enhanced the expression and nuclear translocation of Forkhead box O3 (FOXO3a) via upstream c-Jun N-terminal kinase, inducing the expression of FOXO3a and its target genes, including p21, p27, and Bim. This process led to the reduction of cyclin D1 and enhancement of activated caspase-3 expression. The addition of NAC markedly reversed these effects, knockdown of FOXO3a using small interfering RNA also decreased CD-induced G2/M arrest and apoptosis. In vivo, CD efficiently suppressed the g...Continue Reading
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Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis