Limonene and perillyl alcohol are the naturally occurring monoterpenes found commonly in plant fruits and vegetables. Perillyl alcohol (POH) elicited anticarcinogenic effects in a number of cancer models and pharmacokinetic studies in humans revealed that perillic acid (PA) is the major circulating metabolite following POH administration. Effects of these monoterpenes combined with and without radiation on human head and neck squamous cell carcinoma cell lines (HNSCC) were measured using cytotoxicity and flow cytometry assays. HNSCC cells were pretreated with 1.0 mM PA or 0.5mM POH for 72 hr before exposure to 1Gy or 2Gy radiation dose. Pretreatment with 1.0mM PA or 0.5mM POH sensitized the cells to radiation, causing growth inhibition in HTB-43 (50% and 71%), SCC-25 (55% and 68%) and BroTo (18% and 53%) cells, respectively. PA induced cell-cycle arrest in G0/G1 phase, caused cell death via apoptosis and a reduction in p53 protein in SCC-25 cells.
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