The melanocortin receptors (MCRs 1-5) are G protein coupled-receptors (GPCRs) that regulate food intake, inflammation, skin pigmentation, sexual function and steroidogenesis. Their peptide ligands, the melanocortins, are α-, β- and γ-melanocyte-stimulating hormone and adrenocorticotropic hormone (ACTH) all of which are secreted from the anterior pituitary gland under hypothalamic control. MC2R binds ACTH but has no affinity for the other melanocortins and is, thereby, pharmacologically different from MCRs that bind those ligands. Evidence suggests that elevated GPCRs transactivate the androgen receptor (AR), the critical mediator of prostate cell growth, and consequently promote prostate cancer cell proliferation. It may be that reduced central melanocortin signaling is coincidental with reversal of prostate cancer cachexia, but no data are available on the expression of, or the role for, MCRs in prostate cancer. Here, we show that MCR (1-5) mRNAs are expressed in androgen-dependent LNCaP and androgen-independent PC3 and DU-145 human prostate cancer cell lines. Further, MC2R, the specific target of ACTH, is expressed in LNCaP, PC3 and DU-145 cells. Among the several synthetic MCR peptide ligands that we used, only ACTH promoted concentration-dependent cell proliferation in the three cell lines as shown by MTT cell proliferation assay. In LNCaP cells, the effect was additive with testosterone stimulation and was partially blunted with SHU9119, a non-selective MCR antagonist. In the same cells, ACTH induced cAMP production and increased AR nuclear labeling in immunocytochemical assays. Our observations suggest that MC2R is involved in prostate carcinogenesis and that targeting MC2R signaling may provide a novel avenue in prostate carcinoma treatment.
Natural agents such as curcumin may have the potential to enhance disease resistance in aquaculture. In this study, 30 catfish (Ictalurus punctatus), 2 years of age, were allotted to one of 3 treatment groups (n = 10) to receive diets supplemented with 0.0, 0.5, or 1.0% curcumin. Body weights and lengths of fish were taken at 0, 20, 40 and 60 days after starting the fish on experimental diets. At 60 days, blood samples were collected from 9 fish of each group and then were challenged with Aeromonas hydrophila (0.1 mL of 9×10 6 CFU/mL) intra-peritoneally. Morbidity and mortality was observed daily for 7 days following challenge. Serum separated from blood samples was analyzed for the cytokines, interleukin-4 (IL-4) and interleukin-12 (IL-12). Results indicated significantly higher body weights and lengths but lower levels of both IL-4 and IL-12 with curcumin at 0.5 and 1.0% than the control group. At 24 h following challenge with A. hydrophila, mortality was100 (9/9), 33 (3/9) and 22% (2/9) in the fish supplemented with 0.0, 0.5 and 1.0% curcumin, respectively. At 48 h following challenge, two more fish in the 0.5% group died but the fish remaining in 1.0% group survived even after 7 days. Results of this study suggest that curcumin has the potential to enhance performance of catfish and increase their disease resistance which may help in reducing use of antimicrobials in fish farming.
Standard of nutrient requirements especially amino acid requirements in kampung chickenTingginya harga ayam kampung ini, salah satunya disebabkan oleh pertum buhannya yang lambat, sehingga membutuhkan ransum yang lebih banyak daripada ayam broiler, sehingga angka konversi ransum menjadi lebih besar (efisiensi ransum rendah). Untuk mendapatkan pertambahan berat badan satu kilogram saja, ayam kampung membutuhkan ransum lebih dari 2,8 kg, sementara ayam broiler hanya 1,7 kg. Salah satu cara meningkatkan efisiensi ransum adalah
Docetaxel (DTX) is the treatment of choice for metastatic castration-resistant prostate cancer. However, developing drug resistance is a significant challenge for achieving effective therapy. This study evaluated the anticancer and synergistic effects on DTX of four natural compounds (calebin A, 3′-hydroxypterostilbene, hispolon, and tetrahydrocurcumin) using PC-3 androgen-resistant human prostate cancer cells. We utilized the CellTiter-Glo® luminescent cell viability assay and human PC-3 androgen-independent prostate cancer cells to determine the antiproliferative effects of the four compounds alone and combined with DTX. Cytotoxicity to normal human prostate epithelial cells was tested in parallel using normal immortalized human prostate epithelial cells (RWPE-1). We used cell imaging and quantitative caspase-3 activity to determine whether these compounds induce apoptosis. We also measured the capacity of each drug to inhibit TNF-α-induced NF-kB using a colorimetric assay. Our results showed that all four natural compounds significantly augmented the toxicity of DTX to androgen-resistant PC-3 prostate cancer cells at IC50. Interestingly, when used alone, each of the four compounds had a higher cytotoxic activity to PC-3 than DTX. Mechanistically, these compounds induced apoptosis, which we confirmed by cell imaging and caspase-3 colorimetric assays. Further, when used either alone or combined with DTX, the four test compounds inhibited TNF-α-induced NF-kB production. More significantly, the cytotoxic effects on normal immortalized human prostate epithelial cells were minimal and non-significant, suggesting prostate cancer-specific effects. In conclusion, the combination of DTX with the four test compounds could effectively enhance the anti-prostate cancer activity of DTX. This combination has the added value of reducing the DTX effective concentration. We surmise that calebin A, 3′-hydroxypterostilbene, hispolon, and tetrahydrocurcumin were all excellent drug candidates that produced significant antiproliferative activity when used alone and synergistically enhanced the anticancer effect of DTX. Further in vivo studies using animal models of prostate cancer are needed to confirm our in vitro findings.
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