The quinazoline derivative, 04NB-03, induces cell cycle arrest and apoptosis in hepatocellular carcinoma cells in a reactive oxygen species-dependent manner

Reduction-sensitive polymeric carrier for the targeted delivery of a quinazoline derivative for enhanced generation of reactive oxygen species against cancer

“…The activated caspase-3 cleaves many proteins including c-caspase-3 and PARP. 15 The results show that the free Qd04 and Qd04-SSNPs treatment groups induced much higher c-caspase-3 and PARP levels than the control and blank SSNPs groups, showing stronger caspase activation (Fig. 4G).…”

“…All four treatment groups were intravenously injected via the tail vein, and the drug dose was 2.5 mg kg −1 based on our previous study. 15 Free Qd04 was dissolved in a mixed solution of 5% DMSO, 7.5% Cremophor EL, 7.5% absolute ethanol and 80% normal saline. All mice in four treatment groups were injected every three days, and the body weights and tumor volumes of the mice were recorded during the administration period.…”

“…Previous studies revealed that Qd04 promotes apoptosis in tumor cells mainly by inducing the accumulation of endogenous ROS. 15 Thus, the Qd04-SSNPs nanodrug will effectively respond to and deplete GSH in tumor cells due to the presence of disulfide bonds, which may lead to an imbalance of redox levels in tumor cells and inhibit cellular resistance to Qd04, consequently enhancing the apoptotic effect of ROS on tumor cells. To explore this hypothesis, we detected the intracellular ROS level after various treatments.…”

“…Recently, a novel quinazoline derivative of 04NB-03 (Qd04) has been revealed to exert potent anti-cancer effects against HCC both in vitro and in vivo by our colleagues. 15 Qd04 effectively inhibits the viability and proliferation of HCC cells by inducing cycle arrest and apoptosis in a reactive oxygen species (ROS)-dependent way. In addition, the drug shows no obvious side-effects in living organisms, making it a potential clinical anti-HCC drug.…”

“…In addition, the drug shows no obvious side-effects in living organisms, making it a potential clinical anti-HCC drug. 15 However, the in vivo utilization and further clinical application of Qd04 are impeded by its high hydrophobicity and low bioavailability. Moreover, Qd04 kills tumor cells by inducing the accumulation of endogenous ROS, since abnormal elevation of intracellular ROS levels can induce oxidative stress, which oxidatively damages biomolecules such as proteins and nucleic acids, and thereby induces apoptosis.…”