The chalcone derivative HymnPro generates reactive oxygen species through depletion of intracellular glutathione
2016
Lee, Kyungho | Lee, Da Hyun | Kim, Ji-Ho | Jung, You Jung | Shin, Soon Young | Koh, Dongsoo | Lee, Young Han
2-Hydroxy-4-methoxy-2′,3′-benzochalcone (HymnPro), a chalcone derivative, induces cell cycle arrest at the G2/M phase followed by caspase-dependent apoptosis. Structurally, HymnPro contains a α-β olefin that can act as a Michael acceptor, and that is involved in the depletion of cellular glutathione. However, the effect of HymnPro on the generation of reactive oxygen species (ROS) is still unknown. In the present study, we observed that treatment of Capan-1 pancreatic cancer cells with HymnPro resulted in a dose-dependent accumulation of ROS, owing to the depletion of intracellular glutathione. Treatment with ROS scavenger N-acetylcycteine prevented HymnPro-induced caspase activation and cell death, but had little effect on G2/M cell cycle arrest and microtubule assembly. Our results suggest that HymnPro causes tubulin binding-mediated cell cycle arrest at the G2/M phase as well as ROS-mediated caspase activation.
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