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Volume 4
Toxicology: Open Access
ISSN: 2476-2067
Toxicology Congress 2018
March 12-14, 2018
March 12-14, 2018 Singapore
14
th
World Congress on
Toxicology and Pharmacology
HZ-6d targeted HERC5 to regulate p53 ISGylation in human hepatocellular carcinoma
Lei Zhang
Anhui Medical University, China
M
anipulating the posttranslational modulator of p53 is central in the regulation of its activity and function. ISGylated
p53 can be degraded by the 20S proteasome. During this process, HERC5/Ceb1, an IFN-induced HECT-type E3
ligase, mediated p53 ISGylation. In this study, we indicated that HERC5 was over-expressed in both HCC tissue samples and
cell lines. Knockdown of HERC5 significantly induced the expression of p53, p21 and Bax/Bcl-2 in HCC cells, resulting in
apoptosis augment. Whereas, opposite results were obtained by using HERC5 over-expression. On this basis, we screened a 7,
11-disubstituted quinazoline derivative HZ-6d that could bind to the HERC5 G-rich sequence
in vitro
. Interestingly, HZ-6d
injection effectively delayed the growth of xenografts in nude mice.
In vitro
, HZ-6d significantly inhibited cell growth, suppressed
cell migration, induced apoptosis in HCC cells. Further studies demonstrated the anti-cancer effect of HZ-6d was associated
with down-regulation of HERC5 and accumulation of p53. Collectively, we demonstrated that HZ6d is a HERC5 G-quadruplex
ligand with anti-tumor properties, an action that may offer an attractive idea for restoration of p53 function in cancers.
Recent Publications
1. Wang Y, Ding Q, Xu T, Zhang L (2017) HZ-6d targeted HERC5 to regulate p53 ISGylation in human hepatocellular
carcinoma.
Toxicology & Applied Pharmacology
; 334.
2. Du Y, Li J, Xu T, Zhang L (2017) MicroRNA-145 induces apoptosis of glioma cells by targeting BNIP3 and Notch signaling.
[J]. Oncotarget;
8(37): 61510.
zhanglei-1@ahmu.edu.cnLei Zhang, Toxicol Open Access 2018, Volume 4
DOI: 10.4172/2476-2067-C1-006