Antiproliferative chromone derivatives induce K562 cell death through endogenous and exogenous pathways

摘要

A series of furoxan derivatives of chromone were prepared. The antiproliferative activities were testedagainst five cancer cell lines HepG2, MCF-7, HCT-116, B16, and K562, and two normal human cell lines L02and PBMCs. Among them, compound 15a exhibited the most potent antiproliferative activity. It wasalso found 15a produced more than 8 mM of NO at the peak time of 45 min by Griess assay. Generally,antiproliferative activity is positively related to NO release to some extent. Further in-depth studies onapoptosis-related mechanisms showed that 15a caused S-phase cell cycle arrest in a concentrationdependentmanner and induced apoptosis significantly through mitochondria-related pathways. Humanapoptosis protein array assay also demonstrated 15a increased the expression levels of pro-apoptotic Bax,Bad, HtrA2 and Trail R2/DR5. The expression of catalase and cell cycle blocker claspin were similarly upregulated.In balance, 15a induced K562 cells death through both endogenous and exogenous pathways.