Chalcones with electron-withdrawing and electron-donating substituents: Anticancer activity against TRAIL resistant cancer cells, structure–activity relationship analysis and regulation of apoptotic proteins

• Anticancer activity of chalcones on array of TRAIL-resistant human cancer cells.
• Structure–activity relationship analysis of chalcones anticancer activity.
• Regulation of apoptotic proteins in HT-29 cells challenged with chalcone.

In the present study, a series of 46 chalcones were synthesised and evaluated for antiproliferative activities against the human TRAIL-resistant breast (MCF-7, MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29), nasopharyngeal (CNE-1), erythromyeloblastoid (K-562) and T-lymphoblastoid (CEM-SS) cancer cells. The chalcone 38 containing an amino (-NH2) group on ring A was the most potent and selective against cancer cells. The effects of the chalcone 38 on regulation of 43 apoptosis-related markers in HT-29 cells were determined. The results showed that 20 apoptotic markers (Bad, Bax, Bcl-2, Bcl-w, Bid, Bim, CD40, Fas, HSP27, IGF-1, IGFBP-4, IGFBP-5, Livin, p21, Survivin, sTNF-R2, TRAIL-R2, XIAP, caspase-3 and caspase-8) were either up regulated or down regulated.

Chalcones containing the diverse electron-donating and -withdrawing groups were prepared and evaluated for in vitro antitumour activities. Apoptotic mechanisms induced by the most potent chalcone in the most sensitive HT-29 cancer cell was examined.Figure optionsDownload as PowerPoint slide