"Therefore, agents that sensitize malignant cells to TRAIL-mediated cell death might be of particular importance for the development of novel anti-tumor therapeutic regimens," said lead researcher Vladimir M. Kolenko M.D., Ph.D.
Selenium, a non-metallic trace element essential to human health, could be just that agent.
"Selenium and vitamin E are the most promising dietary supplements considered for use in the reduction of prostate cancer risk," Kolenko said. "This enthusiasm is reflected in the initiation of the large National Cancer Institute sponsored trial - SELECT (Selenium and Vitamin E Chemoprevention Trial). The epidemiologic studies within SELECT will be based on 32,000 men."
With this in mind, Kolenko and colleagues went a step further and studied the effect of methylseleninic acid (MSA), a novel selenium metabolite, in inducing apoptosis in different types of prostate cancer cells (androgen-dependent LNCaP and androgen-independent, PC-3 and DU-145).
"The cytotoxic effect of TRAIL in combination with MSA in LNCaP and DU-145 cells was evaluated using a DNA fragmentation assay," Kolenko explained. "Treatment of prostate cancer cells with TRAIL alone for 24 hours induced negligible levels of apoptosis. Treatment with MSA alone also failed to induce a significant level of cell death in LNCaP cells, although it induced notable apoptosis in DU-145. However, concomitant treatment with TRAIL and MSA resulted in profound DNA fragmentation in both LNCaP and DU-145 cells" (74.3% and 61.5% correspondingly).
"Taken together our data reveal a potential mechanism for the synergistic effect of TRAIL and MSA on the induction of apoptosis in prostate cancer cells," Kolenko concluded. "The combination of TRAIL and MSA may be a novel strategy for the development of innovative therapeutic modalities targeting apoptosis-resistant forms of prostate cancer."
In addition to Kolenko, Fox Chase study authors include visiting scientist Kenya Yamaguchi, M.D., Ph.D., urologic surgical oncologist Robert G. Uzzo, M.D., summer assistant Julia Pimkina and postdoctoral associates Peter Makhov, Ph.D., and Konstantin Golovin, Ph.D.
Fox Chase Cancer Center was founded in 1904 in Philadelphia as the nation's first cancer hospital. In 1974, Fox Chase became one of the first institutions designated as a National Cancer Institute Comprehensive Cancer Center. Fox Chase conducts basic, clinical, population and translational research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at www.fccc.edu or call 1-888-FOX CHASE.