Researchers at Fox Chase Cancer Center in Philadelphia have come a step closer to understanding selenium's molecular role in causing prostate cancer cells to self-destruct. According to data presented today at the 96th Annual Meeting of the American Association for Cancer Research in Anaheim, Calif., selenium helps malignant cells overcome their resistance to TRAIL-induced apopstosis (self-inflicted cell death). Previous studies had shown that TRAIL, a cytotoxic agent being investigated as a new therapeutic agent for cancer, causes malignant cells to self-destruct. Yet some cells resist the treatment.
"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."
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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