Abstract 3612: Study of the functional importance of PPARγ in honokiol-induced apoptosis of hepatoma cells

Hepatocellular carcinoma (HCC) is the leading cause of death in male cancer patients in Asia. PPARγ exhibited an inhibitory role in hepatocarcinogenesis in vitro and in vivo. Recently, it was found that honokiol functions not only as a RXR agonist but also a PPARγ agonist, and is capable of potentiating the activation of PPARγ in the presence of PPARγ agonist rosiglitazone in HLE human hepatoma cells. It also has been reported that honokiol exerts inhibitory effects on the growth and migration in hepatoma cells. However, whether PPARγ overexpression modulates the honokiol-induced growth inhibition in hepatoma cells is not known. Firstly, we examined the expression of PPARγ in tumor samples from 83 HCC patients by immunohistochemical staining. Our results showed that 53 samples had no PPARγ and the clinical parameters including tumor number, stages, and macroscopic vascular invasion (MVI) showed significant negative correlation with PPARγ expression. However, the expression of PPARγ was not associated with disease free survival or overall survival of patients with HCC. Using PPARγ overexpressed SK-Hep1 cells (SK-Hep1-PPARγ) for in vitro analyses, we found that 40 μM honokiol treatment of SK-Hep1-PPARγ cells induced a 20% increase of growth inhibition at 48 hour as compared to vector control cells by MTT assay. This corresponded well with the 15% increase in G0/G1 phase after honokiol treatment at 24 hour compared to vector control cells. In addition, honokiol treatment resulted in decreased cyclin D1, increased p21 and KLF4 expressions in SK-Hep1-PPARγ cells. Moreover, miRNA array analyses showed that increased expression of miR-222, let-7i, miR-628-3p and miR-664 as well as decreased miR-1291, miR184 and miR1249 were observed in SK-Hep1-PPARγ cells. In conclusion, PPARγ is not only a biomarker for prognosis of patients with HCC but also play an important role in the honokiol-induced growth inhibition of hepatoma cells. The functional importance of PPARγ regulated miRNA is currently under further investigation. Citation Format: Chin-Wen Chi, Hui-Tzu Hsu, Jia-Dong Hou, Chih-Chun Lee, Ying-Ju Kuo, Hsin-Chen Lee, Cheng-Yuan Hsia. Study of the functional importance of PPARγ in honokiol-induced apoptosis of hepatoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3612. doi:10.1158/1538-7445.AM2015-3612