Honokiol, a constituent of oriental medicinal herb magnolia officinalis, inhibits growth of PC-3 xenografts in vivo in association with apoptosis induction.

Abstract

PURPOSE:

This study was undertaken to determine the efficacy of honokiol, a constituent of oriental medicinal herb Magnolia officinalis, against human prostate cancer cells in culture and in vivo.

EXPERIMENTAL DESIGN:

Honokiol-mediated apoptosis was assessed by analysis of cytoplasmic histone-associated DNA fragmentation. Knockdown of Bax and Bak proteins was achieved by transient transfection using siRNA. Honokiol was administered by oral gavage to male nude mice s.c. implanted with PC-3 cells. Tumor sections from control and honokiol-treated mice were examined for apoptotic bodies (terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay), proliferation index (proliferating cell nuclear antigen staining), and neovascularization (CD31 staining). Levels of Bcl-2 family proteins in cell lysates and tumor supernatants were determined by immunoblotting.

RESULTS:

Exposure of human prostate cancer cells (PC-3, LNCaP, and C4-2) to honokiol resulted in apoptotic DNA fragmentation in a concentration- and time-dependent manner irrespective of their androgen responsiveness or p53 status. Honokiol-induced apoptosis correlated with induction of Bax, Bak, and Bad and a decrease in Bcl-xL and Mcl-1 protein levels. Transient transfection of PC-3 cells with Bak- and Bax-targeted siRNAs and Bcl-xL plasmid conferred partial yet significant protection against honokiol-induced apoptosis. Oral gavage of 2 mg honokiol/mouse (thrice a week) significantly retarded growth of PC-3 xenografts without causing weight loss. Tumors from honokiol-treated mice exhibited markedly higher count of apoptotic bodies and reduced proliferation index and neovascularization compared with control tumors.

CONCLUSION:

Our data suggest that honokiol, which is used in traditional oriental medicine for the treatment of various ailments, may be an attractive agent for treatment and/or prevention of human prostate cancers.

• Authors: Eun-Ryeong Hahm, Julie A Arlotti, Stanley W Marynowski, Shivendra V Singh
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 4 Pg. 1248-57 (Feb 15 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18281560 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents, Phytogenic
• Biphenyl Compounds
• Lignans
• Mcl1 protein, mouse
• Myeloid Cell Leukemia Sequence 1 Protein
• Neoplasm Proteins
• Proto-Oncogene Proteins c-bcl-2
• bcl-2 Homologous Antagonist-Killer Protein
• bcl-2-Associated X Protein
• bcl-Associated Death Protein
• bcl-X Protein
• honokiol

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Biphenyl Compounds (pharmacology)
• Cell Line, Tumor
• Humans
• Immunoblotting
• Lignans (pharmacology)
• Magnolia (chemistry)
• Male
• Mice
• Mice, Nude
• Myeloid Cell Leukemia Sequence 1 Protein
• Neoplasm Proteins (drug effects, metabolism)
• Prostatic Neoplasms (drug therapy, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (drug effects, metabolism)
• bcl-2 Homologous Antagonist-Killer Protein (drug effects, metabolism)
• bcl-2-Associated X Protein (drug effects, metabolism)
• bcl-Associated Death Protein (drug effects, metabolism)
• bcl-X Protein (drug effects, metabolism)