December 1, 2008
Biomedical research has long been largely a tale of scientific disciplines, each following its own analytical path and pursuing its own distinct set of diseases. But these disciplines, like musical genres, influence each other and often unexpectedly. Take the case of the natural compound farnesol. Farnesol is a key intermediate in the synthesis of cholesterol in mammalian cells. Over the last two decades, scientists have learned that large doses of farnesol kill certain tumor cells, causing them to undergo programmed cell death (apoptosis). More recently, scientists identified farnesol as a quorum sensing molecule produced by Candida albicans, the most common pathogenic fungal species for humans. Farnesol was shown to inhibit the ability of C. albicans to adhere to surfaces or form biofilms, a property crucial to its pathogenesis.
These two strands of investigation have recently converged to identify an unlikely association between this fungal-produced quorum sensing molecule and human oral squamous carcinoma cells. As published in the September issue of the journal Neoplasia, a team of NIDCR-supported researchers had demonstrated in their previous studies that C. albicans modulates its production of farnesol and, at high concentrations the compound can kill the fungal cell. These findings led to in depth investigations to determine whether the farnesol produced by C. albicans as it grows in a biofilm exerts an apoptotic effect on the cancer cells. By analyzing apoptotic markers and through global proteomic analyses, the scientists compared the effects of fungal and synthetic forms of farnesol on the cancer cells. The findings demonstrated for the first time that C. albicans-secreted farnesol can inhibit tumor cell growth by triggering apoptosis through the same cellular apoptotic pathways as its synthetic counterpart. Sifting through their datasets for further details, the researchers analyzed 36 differentially expressed proteins following treatment, of which 25 were positively identified. Interestingly, of the 26 up-regulated proteins, many already were known to play a role in inhibiting cancer, metabolism, and protein binding and folding. Of the 10 down-regulated proteins, several were known to inhibit apoptosis, while others are frequently over-expressed in epithelial carcinomas. “Future studies using our proteomic analysis could potentially delineate how farnesol preferentially targets transformed cells,” the authors noted. Active investigations are currently underway in their laboratories to evaluate the therapeutic potential of farnesol as an anti-tumor agent.
- Read more about this study by Scheper MA, Shirtliff ME, Meiller TA, Peters BM, and Jabra-Rizk MA