IADR Abstract Archives
Anti-Tumor Effects of Thymol in Oral Squamous Cell Carcinoma
Objectives: Oral squamous cell carcinoma (OSCC) represents 90% of all oropharyngeal cancers. Advanced disease has a poor five-year overall survival rate (~35%) that has not changed in nearly 40 years. Thymol was identified as having significant cytotoxic effects from a screening of plant extracts against numerous cancer cell lines. Thymol, a major component of thyme and oregano, is also found in oral health care products, such as Listerine. It is a known agonist for Transient Receptor Potential (TRP) ion channels (TRPA1 and weakly, TRPM8 and TRPV1) whose activation is hypothesized to result in increased intracellular calcium and subsequent apoptosis. Our preliminary data indicates that TRPA1 is not expressed in OSCC yet Thymol retains its cytotoxicity. Our purpose is to evaluate Thymol for its anti-tumor effects in OSCC in vitro and in vivo, and determine if the cytotoxic effects of Thymol are due to TRP channel activation or a novel mechanism-of-action.
Methods: Immunofluorescent staining and reverse transcription polymerase chain reaction (RT-PCR) were used to detect expression of TRP channels in OSCC cell lines. The effect of Thymol on OSCC was demonstrated using cell viability assays and mouse OSCC xenograft models. Calcium imaging was used to determine if Thymol activates TRP channels in OSCC.
Results: The absence of TRPA1 expression and presence of TRPM8 and TRPV1 was confirmed via immunofluorescent staining and RT-PCR analyses of OSCC cell lines. Cell viability assays showed a dose-dependent cytotoxic response of OSCC to Thymol. Intra-tumor administration of Thymol every other day for two weeks significantly inhibited SCC4 tumor growth in vivo. Calcium imaging revealed the absence of TRP channel activation in SCC4 cells.
Conclusions: Thymol has significant anti-tumor effects in OSCC via a novel mechanism-of-action that is independent of TRP channel activation. Additional studies evaluating this novel mechanism and developing Thymol as a potential treatment for oral cancer are underway.
Methods: Immunofluorescent staining and reverse transcription polymerase chain reaction (RT-PCR) were used to detect expression of TRP channels in OSCC cell lines. The effect of Thymol on OSCC was demonstrated using cell viability assays and mouse OSCC xenograft models. Calcium imaging was used to determine if Thymol activates TRP channels in OSCC.
Results: The absence of TRPA1 expression and presence of TRPM8 and TRPV1 was confirmed via immunofluorescent staining and RT-PCR analyses of OSCC cell lines. Cell viability assays showed a dose-dependent cytotoxic response of OSCC to Thymol. Intra-tumor administration of Thymol every other day for two weeks significantly inhibited SCC4 tumor growth in vivo. Calcium imaging revealed the absence of TRP channel activation in SCC4 cells.
Conclusions: Thymol has significant anti-tumor effects in OSCC via a novel mechanism-of-action that is independent of TRP channel activation. Additional studies evaluating this novel mechanism and developing Thymol as a potential treatment for oral cancer are underway.