Combined effect of honokiol and rosiglitazone on cell growth inhibition through enhanced G0/G1 phase arrest in hepatoma cells. Issue 8 (August 2016)

• Record Type: Journal Article
• Authors: Chen, Hsiao‐Chi; Hsu, Hui‐Tzu; Weng, Jing‐Wen; Chang, Yuh‐Fang; Hsia, Cheng‐Yuan; Lee, Hsin‐Chen; Chi, Chin‐Wen
• Is Part Of: Journal of the Chinese Medical Association. Volume 79:Issue 8(2016)
• Publication Date: 2016-08
• Subjects: hepatocellular carcinoma -- honokiol -- PPARγ agonist -- rosiglitazone; Medicine -- Periodicals; 610.5
• DOI: 10.1016/j.jcma.2016.03.003
• Languages: English
• ISSNs: 1726-4901

Abstract

Abstract : Background : Honokiol, a derivative extracted from the stem and bark of Magnolia officinalis, has been reported to have anticancer effects in hepatoma cells. Recently, it was found that honokiol acted as not only a retinoid X receptor (RXR) agonist but also as a peroxisome proliferator‐activated receptor gamma (PPARγ) agonist. Additionally, honokiol is capable of activating PPARγ/RXR heterodimers synergistically in the presence of rosiglitazone in 3T3‐L1 adipocyte and HLE human hepatoma cells. Furthermore, synthetic PPARγ agonist thiazolidinediones exhibited growth inhibition effects in hepatoma cells through PPARγ‐dependent and PPARγ‐independent pathways. However, the combined effects of treatment with honokiol and PPARγ agonist are unclear in hepatoma cells. Methods : In this study, sulforhodamine B assay, flow cytometry, and Western blot analysis were used to examine the combined effects of honokiol and PPARγ agonist (rosiglitazone) treatment on growth inhibition in SK‐Hep1 and Mahlavu hepatoma cells. Results : Honokiol or rosiglitazone treatment in hepatoma cells induced growth inhibition at high dose by sulforhodamine B assay. Moreover, we found that combined treatment with honokiol and rosiglitazone showed more effective growth inhibition in hepatoma cells than treatment with honokiol or rosiglitazone alone. Also, treatment with honokiol and rosiglitazone induced cell cycle arrest in the G0/G1 phase; increased p21; and decreased cyclin D1, cyclin E1, and Rb expression in SK‐Hep1 hepatoma cells. Conclusion : Honokiol combined with rosiglitazone showed more effective growth inhibition in hepatoma cells mediated through the regulation of G0/G1 phase‐related proteins p21, cyclin D1, cyclin E1, and Rb and cell cycle progression.