| Title | LRD-22, a novel dual dithiocarbamatic acid ester, inhibits Aurora-A kinase and induces apoptosis and cell cycle arrest in HepG2 cells |
| Authors | Wang, Huiling Li, Ridong Li, Li Ge, Zemei Zhou, Rouli Li, Runtao |
| Affiliation | Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. Peking Univ, Dept Cell Biol, Sch Basic Med Sci, Beijing 100191, Peoples R China. Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, 38 Xueyuan Rd, Beijing 100191, Peoples R China. |
| Keywords | Dual dithocarbamatic acid ester HepG2 cell Apoptosis Cell cycle p53 Aurora-A P53 DERIVATIVES COMPLEXITY |
| Issue Date | 2015 |
| Publisher | 生物化学与生物物理学研究通讯 |
| Citation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2015,458,(1),201-207. |
| Abstract | In this study we investigated the antitumor activity of the novel dual dithiocarbamatic acid ester LRD-22 in vitro and in vivo. Several cancer cell lines were employed to determine the effect of LRD-22 on cell growth, and the MIT assay showed there was a significant decrease in viable tumor cell numbers in the presence of LRD-22, especially in the HepG2 cell line. Colony formation assay also showed LRD-22 strongly inhibits HepG2 cell growth. Evaluation of the mechanism involved showed that inhibitory effects of LRD-22 on cell growth are due to induction of apoptosis and G2/M arrest. LRD-22 inhibited Aurora-A phosphorylation at Thr(288) and subsequently impaired p(53) phosphorylation at Ser(315) which was associated with the proteasome degradation pathway. Tumor suppressor protein p53 is stabilized by this mechanism and accumulates through inhibition of Aurora-A kinase activity via treatment with LRD-22. In vivo study of HepG2 xenograft in nude mice also shows LRD-22 suppresses tumor growth at a concentration of 5 mg/kg without animals suffering loss of body weight. In conclusion, our results demonstrate LRD-22 acts as an Aurora-A kinase inhibitor to induce apoptosis and inhibit proliferation in HepG2 cells, and should be considered as a promising targeting agent for HCC therapy. (C) 2015 Elsevier Inc. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/156271 |
| ISSN | 0006-291X |
| DOI | 10.1016/j.bbrc.2015.01.102 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 药学院 基础医学院 天然药物与仿生药物国家重点实验室 |
