Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2005; 11(19): 2927-2931
Published online May 21, 2005. doi: 10.3748/wjg.v11.i19.2927
Cytotoxic effect of a non-peptidic small molecular inhibitor of the p53-HDM2 interaction on tumor cells
Wen-Dong Li, Mi-Juan Wang, Fang Ding, Da-Li Yin, Zhi-Hua Liu
Wen-Dong Li, Fang Ding, Zhi-Hua Liu, National Laboratory of Molecular Oncology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China
Mi-Juan Wang, Da-Li Yin, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Zhi-Hua Liu, Professor, National Laboratory of Molecular Oncology, Cancer Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100021, China. liuzh@pubem.cicams.ac.cn
Telephone: +86-10-67723789 Fax: +86-10-67723789
Received: May 27, 2004
Revised: May 28, 2004
Accepted: June 17, 2004
Published online: May 21, 2005
Abstract

AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.

METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.

RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.

CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.

Keywords: Non-peptidic small molecular weight inhibitors; Cytotoxic effect; p53; Cancer therapy; HDM2