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Methylseleninic Acid (methylseleninic + acid)
Selected AbstractsMethylseleninic acid enhances the effect of etoposide to inhibit prostate cancer growth in vivoINTERNATIONAL JOURNAL OF CANCER, Issue 6 2007Oscar Gonzalez-Moreno Abstract New therapeutic agents are needed for the treatment of androgen-independent prostate cancer (PrCa). We have investigated the effect of methylseleninic acid (MSA) on tumor stage-specific prostate cells derived from the C3 (1)/Tag model for PrCa: Pr111, a slow-growing and nontumorigenic cell line isolated from a prostate intraepithelial neoplasia lesion; Pr14, a tumorigenic line derived from a primary tumor; and Pr14C1, a sub-clone of Pr14 explanted from a lung metastasis. We demonstrate that MSA strongly inhibits cell growth and induces apoptosis in C3 (1)/Tag tumor cells, in a dose-dependent manner. A decrease in phosphorylated ERK1/2 and AKT was also found in tumor cells, but not in Pr111. Microarray analysis using affymetrix showed that the number of genes with an altered expression in tumor cells is significantly higher (p < 0.01) than in nontumoral cells. Pathways analyses revealed a decrease in the expression of genes involved in metabolism (Fabp5, Cyba), signal transduction (ERK, AKT), angiogenesis (neuropilin-1, Flt-4) and transcription (cAMP response element-binding protein) in tumor cells. The expression of neuropilin-1, a protein involved in VEGF signaling and tumor angiogenesis, was 97-fold repressed in Pr14 cells treated with MSA. Combination treatments using low doses of etoposide or taxotere (docetaxel), plus low doses of MSA revealed a strong enhancement of cell growth inhibition and apoptosis in tumor cells. Our in vivo studies using Pr14 cells xenografted into nude mice demonstrated that MSA significantly enhances the chemotherapeutical effect of etoposide, resulting in 78.3% tumor growth inhibition. These results suggest that MSA could be used against PrCa to enhance the effect of etoposide. © 2007 Wiley-Liss, Inc. [source] Augmented suppression of androgen receptor signaling by a combination of ,-tocopheryl succinate and methylseleninic acidCANCER, Issue 12 2006Haitao Zhang PhD Abstract BACKGROUND. Previous reports showed that ,-tocopheryl succinate (,TS) and methylseleninic acid (MSA) independently reduce the abundance of androgen receptor (AR) in prostate cancer cells. The response to MSA happens quickly, whereas the response to ,TS takes much longer. The present study was designed to investigate whether a combination of ,TS and MSA would produce an additive or a greater than additive effect in suppressing AR level, AR transactivation, and prostate-specific antigen (PSA). METHODS. LNCaP cells were treated with ,TS alone for 31 hours, MSA alone for 3 hours, or ,TS first for 28 hours and ,TS/MSA together for the last 3 hours. AR and PSA mRNA levels were quantitated by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). AR transactivation was determined by the ARE-luciferase reporter assay. Both cellular and secretory PSA was also measured by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS. Different doses of ,TS were evaluated in combination with MSA. Some striking results are highlighted below for ,TS alone, MSA alone, or ,TS/MSA (presented in that order). AR mRNA level was depressed by 0%, 20%, or 60%, respectively; AR transactivation was inhibited by 35%, 10%, or 60%, respectively; whereas the PSA mRNA level was decreased by 40%, 60%, or 90%, respectively. Interestingly, secretory PSA was consistently reduced to a greater extent than cellular PSA. CONCLUSIONS. A combination of ,TS/MSA produced a greater than additive effect in suppressing AR signaling compared with the single agent. Decreased AR abundance is a major factor, but not necessarily the sole factor, in diminishing the transcriptional activity of AR by ,TS or MSA. Cancer 2006. © 2006 American Cancer Society. [source] | ||||||||||