ABSTRACT
BACKGROUND: Approximately 30,000 people are diagnosed with oral cancer annually in the United States. Recent evidence suggests that nutrition may play a more complex role in the prevention of oral cancers than previously believed. Proanthocyanidins (PACs) are a class of compounds found in normal dietary foods that exhibit chemopreventive properties and chemotherapeutic potential. Recently preliminary evidence suggests that PACs inhibit the proliferation of oral cancer cell lines. The primary goal of this study was to elucidate the mechanisms responsible for previous observations that grape seed-derived PACs significantly inhibited oral cancer proliferation. METHODS: Using the well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, as well as nontumorigenic cell lines, a series of in vitro assays was performed to quantify the temporal and dose-specific growth inhibitory properties of PAC on oral cancers. In addition, quantitative analysis of mRNA from key intracellular signaling pathway molecules, involved in both cell-cycle control and apoptosis, were analyzed using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). RESULTS: This study found that oral cancer proliferation was inhibited by 24 hours in the PAC concentration range of 50-70 µg/mL with concomitant decreases in mRNA expression of specific cell-cycle regulators, and increases in the expression of apoptosis-specific molecules, such as caspase-2 and caspase-8. CONCLUSION: These results may represent the first demonstration of simultaneous, temporal inhibition of cell-cycle signaling pathways with the activation of specific apoptosis-related signaling pathways within oral cancers in response to PAC, lending further support to the concept that PACs may be promising candidates for adjuvant or complementary therapies for oral cancer patients.
