Investigational New Drugs

, Volume 27, Issue 3, pp 223–232

Antitumor activity of a novel series of α-aryloxy-α-methylhydrocinnamic acid derivatives as PPAR gamma agonists against a panel of human cancer cell lines

  • Xishan Xiong
  • Yangliang Ye
  • Lili Fu
  • Bing Dai
  • Jieqiong Liu
  • Jieshuang Jia
  • Jing Tang
  • Lin Li
  • Li Wang
  • Jianhua Shen
  • Changlin Mei
PRECLINICAL STUDIES

DOI: 10.1007/s10637-008-9161-0

Cite this article as:
Xiong, X., Ye, Y., Fu, L. et al. Invest New Drugs (2009) 27: 223. doi:10.1007/s10637-008-9161-0

Summary

Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have shown benefit in treating diabetes mellitus, atherosclerosis and cancer. However, widespread use of thiazolidinediones (TZDs), the clinically used synthetic PPARγ agonists, has been limited by adverse cardiovascular effects. Consequently, numerous novel non-TZD compounds were synthesized and antidiabetic efficacy was evaluated to identify PPARγ agonists for potential clinical use. On the other hand, many studies have documented that the antitumor activity of PPARγ agonists is PPARγ independent. Here we hypothesized that there might exist some compounds with less PPARγ agonistic activity or antidiabetic efficacy but potent antitumor activity. In this study, we evaluated the PPARγ agonistic and antitumor activity of several newly synthesized α-aryloxy-α-methylhydrocinnamic acid derivatives as PPARγ agonists in a panel of human cancer cell lines, which showed promising antitumor activity without appreciable PPARγ agonistic activity. The results of MTT assay revealed that cell viability was inhibited in a dose dependent manner with IC50 17.1–55.1 μM for all the novel compounds and rosiglitazone (17.2–165 μM). They induced cell cycle arrest and apoptosis tested by Flow Cytometry. In conclusion, our findings demonstrate that these compounds have potent in vitro cytotoxicity, the possible mechanism of which is through induction of apoptosis and cell cycle arrest

Keywords

Peroxisome proliferator-activated receptor gamma α-aryloxy-α-methylhydrocinnamic acid derivative A549 IC50 Apoptosis Cell cycle 

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Xishan Xiong
    • 1
  • Yangliang Ye
    • 2
  • Lili Fu
    • 1
  • Bing Dai
    • 1
  • Jieqiong Liu
    • 1
  • Jieshuang Jia
    • 1
  • Jing Tang
    • 2
  • Lin Li
    • 1
  • Li Wang
    • 1
  • Jianhua Shen
    • 2
  • Changlin Mei
    • 1
  1. 1.Nephrology institute of PLA, Department of Internal Medicine, Changzheng HospitalSecond Military Medical UniversityShanghaiPeople’s Republic of China
  2. 2.Drug Discovery and Design Centre, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Graduate School of the Chinese Academy of SciencesChinese Academy of SciencesShanghaiPeople’s Republic of China

Personalised recommendations