Inhibition of oral cancer growth in vitro is modulated through differential signaling pathways by over-the-counter proanthocyanidin supplements.

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.

Student-to-student local anesthesia injections in dental education: moral, ethical, and legal issues.

This article reports the findings of a survey-based study conducted to determine U.S. dental schools' institutional protocols regarding the practice of students' administering local anesthetic injections to fellow students as part of their process of learning this skill. The majority of schools ask students to practice local anesthetic injections on each other without obtaining informed consent.

High risk HPV types 18 and 16 are potent modulators of oral squamous cell carcinoma phenotypes in vitro.

BACKGROUND: Human papillomavirus (HPV) has been confirmed as the primary etiological factor that transforms cervical epithelia into cancer. The presence of HPV in oral cancers suggests that HPV may play a similar role in transforming the oral epithelia. A high degree of variability in the prevalence of HPV in oral cancers has been found, however, raising questions regarding its role in the transformation and development of oral cancers. The goal of this study was to test our hypothesis that high-risk HPV strains HPV16 and HPV18 will alter the phenotype of transformed oral squamous cell carcinoma cell lines, CAL27, SCC-15 and SCC-25 in vitro. RESULTS: CAL27 cells transfected with HPV18, HPV16, as well as HPV16/18 co-transfectants, demonstrated significant increases in proliferation, adhesion and cell spreading compared with non-transfected controls. These observed differences were correlated with a small level of increased cell survival. SCC-15 cells, however, displayed a differential response to HPV transfection, with only HPV18-transfectants demonstrated changes to proliferation. Interestingly, SCC-25 cells displayed a more complex response, with HPV16-induced increases in cell proliferation, viability and cell spreading, while HPV18- and 16/18-transfectants exhibited reduced adhesion and proliferation. CONCLUSION: Determining the potential of specific high-risk HPV strains to alter phenotypic behaviors of already transformed oral carcinomas is a critical step in providing more accurate prognosis and treatment options for oral cancer patients. The identification of differential responses to specific HPV strains among oral cancers suggests a more significant, complex and multifactorial role of HPV, not only in transforming, but also in modulating, the phenotype and treatment responsiveness of precancerous and cancerous oral lesions. This study provides some of the first evidence to help identify the important molecular markers for pathways that could be used to determine the most effective and appropriate treatment plans for oral cancer patients with concomitant oral HPV infections.

Oral squamous cell carcinoma proliferative phenotype is modulated by proanthocyanidins: a potential prevention and treatment alternative for oral cancer.

BACKGROUND: Despite the recently reported drop in the overall death rate from cancer, the estimated survival rate and number of deaths from oral cancer remain virtually unchanged. Early detection efforts, in combination with strategies for prevention and risk-reduction, have the potential to dramatically improve clinical outcomes. The identification of non-toxic, effective treatments, including complementary and alternative therapies, is critical if the survival rate is to be improved. Epidemiologic studies have suggested a protective effect from certain plant-derived foods and extracts; however, it has been difficult to isolate and identify the compounds most responsible for these observations. The primary purpose of this study was to investigate the response of human oral squamous cell carcinoma (OSCC) to proanthocyanidin (PAC), a plant-derived compound that may inhibit the progression of several other cancers. METHODS: Using a series of in vitro assays, we sought to quantify the effects of PAC on OSCC, cervical carcinoma, and non-cancerous cell lines, specifically the effects of PAC on cell proliferation. Recent data suggest that infection with the human papillomavirus (HPV) may also modulate the proliferative potential of OSCC; therefore, we also measured the effects of PAC administration on HPV-transfected OSCC proliferation. RESULTS: Our results demonstrated that PAC administration was sufficient to significantly suppress cellular proliferation of OSCC in a dose-dependent manner. In addition, the increased proliferation of OSCC after transfection with HPV 16 was reduced by the administration of PAC, as was the proliferation of the cervical cancer and non-cancerous cell lines tested. Our results also provide preliminary evidence that PAC administration may induce apoptosis in cervical and oral cancer cell lines, while acting merely to suppress proliferation of the normal cell line control. CONCLUSION: These results signify that PAC may be a compelling candidate for testing in both animal and human models. Furthermore, these data provide adequate justification for elucidating the divergent mechanisms of PAC-induced proliferation, inhibition, and apoptosis among these and other cell lines.