Combined effect of honokiol and rosiglitazone on cell growth inhibition through enhanced G0/G1 phase arrest in hepatoma cells.
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.


CONCLUSIONS
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.
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Hsiao-Chi
HC
Chen
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan, ROC.
Hui-Tzu
HT
Hsu
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Jing-Wen
JW
Weng
Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Yuh-Fang
YF
Chang
Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Cheng-Yuan
CY
Hsia
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Hsin-Chen
HC
Lee
Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan, ROC; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address: cwchi@vghtpe.gov.tw.
Chin-Wen
CW
Chi
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D000498:Allyl Compounds; D010636:Phenols
D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D017705:Lignans; D047495:PPAR gamma; D000077154:Rosiglitazone; D045162:Thiazolidinediones; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
PPARγ agonist; hepatocellular carcinoma; honokiol; rosiglitazone