Pochodne pirazolin skondensowane z chromanonem lub flawanonem w terapii raka jelita grubego: analiza molekularnych aktywności przeciwnowotworowych. - Miniatura 7 2023/07/X/NZ3/01404 (dataset)

Abstract

This study investigated the anticancer potential of six flavanone/chromanone derivatives on five human colorectal cancer cell lines (HCT 116, SW620, LoVo, Caco-2, HT-29). Cytotoxicity assays (MTT) revealed that three compounds (1, 3, 5) exhibited significant antiproliferative activity (IC50 ~8–30 µM), comparable to or exceeding cisplatin. These derivatives induced reactive oxygen species (ROS), primarily superoxide anion radicals (O2─•), leading to glutathione (GSH) depletion. Pre-incubation with antioxidants (NAC, vitamin E) attenuated cytotoxicity, confirming ROS’s role.

Mechanistically, the compounds induced both apoptosis (mitochondrial membrane hyperpolarization, caspase-3/9 activation) and autophagy (MDC signal increase). Strong genotoxic effects were observed, evidenced by DNA damage (comet assay) and PARP degradation. Cell cycle analysis showed G2/M arrest. Overall, these derivatives demonstrate promising anticancer potential through ROS induction, DNA damage, and activation of apoptosis/autophagy, suggesting their potential as novel chemotherapeutic agents.