The chalcone derivative HymnPro generates reactive oxygen species through depletion of intracellular glutathione

Abstract

2-Hydroxy-4-methoxy-2 0 ,3 0 -benzochalcone (Hym nPro), a chalcone derivative, induces cell cycle arrest at the G2/M phase followed by caspase-dependent apoptosis. Structurally, HymnPro contains a a-b 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 ROSmediated caspase activation.

A review on synthetic chalcone derivatives as tubulin polymerisation inhibitors

“…The molecular mechanisms showed that compound 20 exerts antitumor activity by disrupting microtubule assembly, which leads to mitotic arrest and sequential activation of the caspase pathway, resulting in apoptosis. In 2016, Lee and colleagues observed that treatment CaPan-1 pancreatic cancer cells with 20 resulted in a dose-dependent accumulation of ROS due to intracellular glutathione depletion 41 . Meanwhile, N-acetylcysteine, a ROS scavenging agent, can inhibit Hymnpro-induced caspase activation and cell death, but G2/M cell cycle arrest and microtubule assembly were not significantly affected.…”

Synthesis, Crystal Structure, Hirshfeld Surface Analysis and Docking Studies of a Novel Flavone–Chalcone Hybrid Compound Demonstrating Anticancer Effects by Generating ROS through Glutathione Depletion

“…Other small molecules as well as Piperlongumine derivatives remove glutathione (GSH) in cancer cells and cause an increase in intracellular ROS [25][26][27][28][29]. Our previous studies demonstrated that the compounds containing the conjugate carbonyl group, such as flavones and chalcones, are essential for GSH removal [30][31][32][33]. The molecular hybridization provides a multi-pharmacophore and becomes a tool more useful than the original compound, for realizing a synergistic drug effect [34].…”