HZ08, a great regulator to reverse multidrug resistance via cycle arrest and apoptosis sensitization in MCF-7/ADM

Long‐Term Alteration of Reactive Oxygen Species Led to Multidrug Resistance in MCF‐7 Cells

“…And the increased Nrf2 and HIF-1 α , in particular, concentrated in the nuclei suggesting them in activation (Figures 9(a), 9(b), and 9(c)). Moreover, it has been well established that the overexpressions of PKC α , c-Myc, and GST π , which, respectively, signify strong ability of ROS scavenging and P-gp overexpression [25, 26], apoptosis resistance and high proliferation [27], and overactivation of cellular detoxification [28], were classic mechanisms of MDR. Therefore, western blot was performed to determine these protein levels in MCF-7/ADM cells and MCF-7 cells with different treatments.…”

“…MDR is a major obstacle to the successful cancer chemotherapy, and it involves various mechanisms, mainly including overexpressed efflux transporters, overactivated detoxification system, and imbalanced apoptosis/proliferation [27]. Since functional crosstalk in the signaling pathways between various phenotypes of MDR has been reported in many MDR cancers [31], it is important for us to identify the common mediator in the signaling pathways among different phenotypes of MDR, which may help us to pinpoint critical targets for a better control of MDR during cancer chemotherapy.…”

“…Several reports suggested that increased levels of PKC isoforms, mainly for PKC α , were found in MDR cells linking with activated P-gp [26]. C-Myc, a prosurvival/antiapoptosis factor, has recently been reported to participate, at least partly, in MDR to some types of cancers [27]. It was established that c-Myc is responsible for directing and coordinating the transcription of MDR transporters in leukemia and human colon carcinoma [50].…”

Reconstituted high density lipoprotein mediated targeted co-delivery of HZ08 and paclitaxel enhances the efficacy of paclitaxel in multidrug-resistant MCF-7 breast cancer cells

“…considerable attention due to its potent MDR reversal effect (Cen et al, 2010) via working as the substrate for P-gp and noncompetitively inhibiting anticancer drug efflux function . Importantly, HZ08 has little effect on normal enzymes .…”

The effect of multidrug resistance modulator HZ08 on pharmacodynamics and pharmacokinetics of adriamycin in xenograft-nude mice

“…1) has a strong ability to reverse P-gp mediated MDR. HZ08 can sensitize K562/A, KBv200 as well as MCF-7/A cells to adriamycin and vincristine (Cen et al, 2010(Cen et al, , 2011Zhu et al, 2012). Furthermore, according to the result of Caco-2 monolayer http://dx.doi.org/10.1016/j.ejps.2014.10.011 0928-0987/Ó 2014 Elsevier B.V. All rights reserved.…”