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Oncotarget. 2015 Aug 28;6(25):21268-82.

Honokiol inhibits the growth of head and neck squamous cell carcinoma by targeting epidermal growth factor receptor.

Author information

1
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA.
2
Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, USA.
3
Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
4
Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA.

Abstract

Here, we report the chemotherapeutic effect of honokiol, a phytochemical from Magnolia plant, on human head and neck squamous cell carcinoma (HNSCC). Treatment of HNSCC cell lines from different sub-sites, SCC-1 (oral cavity), SCC-5 (larynx), OSC-19 (tongue) and FaDu (pharynx) with honokiol inhibited their cell viability, which was associated with the: (i) induction of apoptosis, (ii) correction of dysregulatory cell cycle proteins of G0/G1 phase. Honokiol decreased the expression levels of epidermal growth factor receptor (EGFR), mTOR and their downstream signaling molecules. Treatment of FaDu and SCC-1 cell lines with rapamycin, an inhibitor of mTOR pathway, also reduced cell viability of HNSCC cells. Administration of honokiol by oral gavage (100 mg/kg body weight) significantly (P < 0.01-0.001) inhibited the growth of SCC-1 and FaDu xenografts in athymic nude mice, which was associated with: (i) inhibition of tumor cell proliferation, (ii) induction of apoptosis, (iii) reduced expressions of cyclins and Cdks, and (iv) inhibition of EGFR signaling pathway. Molecular docking analysis of honokiol in EGFR binding site indicated that the chemotherapeutic effect of honokiol against HNSCC is mediated through its firm binding with EGFR, which is better than that of gefitinib, a commonly used drug for HNSCC treatment.

KEYWORDS:

animal model; carcinogenesis; chemotherapy; oncology; prevention; signal transduction; targeted therapy

PMID:
26020804
PMCID:
PMC4673264
DOI:
10.18632/oncotarget.4178
[Indexed for MEDLINE]
Free PMC Article

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