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.