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Honokiol, a constituent of oriental medicinal herb magnolia officinalis, inhibits growth of PC-3 xenografts in vivo in association with apoptosis induction.
Clin Cancer Res. 2008 Feb 15; 14(4):1248-57.CC

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+Show Affiliations

Department of Pharmacology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18281560

Citation

Hahm, Eun-Ryeong, et al. "Honokiol, a Constituent of Oriental Medicinal Herb Magnolia Officinalis, Inhibits Growth of PC-3 Xenografts in Vivo in Association With Apoptosis Induction." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 14, no. 4, 2008, pp. 1248-57.
Hahm ER, Arlotti JA, Marynowski SW, et al. Honokiol, a constituent of oriental medicinal herb magnolia officinalis, inhibits growth of PC-3 xenografts in vivo in association with apoptosis induction. Clin Cancer Res. 2008;14(4):1248-57.
Hahm, E. R., Arlotti, J. A., Marynowski, S. W., & Singh, S. V. (2008). Honokiol, a constituent of oriental medicinal herb magnolia officinalis, inhibits growth of PC-3 xenografts in vivo in association with apoptosis induction. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 14(4), 1248-57. https://doi.org/10.1158/1078-0432.CCR-07-1926
Hahm ER, et al. Honokiol, a Constituent of Oriental Medicinal Herb Magnolia Officinalis, Inhibits Growth of PC-3 Xenografts in Vivo in Association With Apoptosis Induction. Clin Cancer Res. 2008 Feb 15;14(4):1248-57. PubMed PMID: 18281560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Honokiol, a constituent of oriental medicinal herb magnolia officinalis, inhibits growth of PC-3 xenografts in vivo in association with apoptosis induction. AU - Hahm,Eun-Ryeong, AU - Arlotti,Julie A, AU - Marynowski,Stanley W, AU - Singh,Shivendra V, PY - 2008/2/19/pubmed PY - 2008/6/5/medline PY - 2008/2/19/entrez SP - 1248 EP - 57 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 14 IS - 4 N2 - 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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/18281560/Honokiol_a_constituent_of_oriental_medicinal_herb_magnolia_officinalis_inhibits_growth_of_PC_3_xenografts_in_vivo_in_association_with_apoptosis_induction_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=18281560 DB - PRIME DP - Unbound Medicine ER -