Edible-plant derived 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone exert dual effects on invigorating triple-negative breast cancer apoptosis

Abstract

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC) is a typical and abundant chalcone compound from the buds of Cleistocalyx operculatus, which is well-known for its edible and medicinal qualities. In this study, DMC showed effective cell cycle arrest at G₂/M on MDA-MB-231 cells, though dual impacts, including the inhibition of microtubule polymerization through binding to β-tubulin and the stimulation of reactive oxygen species (ROS) production by inhibiting catalase activity. The increased ROS level inhibited PI3K/Akt/mTOR pathway and further suppressed the expression level of Cdc2, Cdc25C, and Cyclin B1, alongside stimulated the expression level of p21 and p27. Above 29.5% MDA-MB-231 cells were arrested at G₂/M phase, subsequently undergoing apoptosis due to heightened levels of apoptosis-related proteins Bax and caspase 3. In summary, this study demonstrated that DMC concomitantly plays dual roles in apoptotic inducing by inhibiting the ROS consumption and microtubules formation in triple-negative breast cancer cells.