, Volume 27, Issue 3, pp 223-232
Date: 13 Aug 2008

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

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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

Xishan Xiong and Yangliang Ye contributed equally to this work.