Diphenyl diselenide supplementation delays the development of N-nitroso-N-methylurea-induced mammary tumors
ABSTRACT The effect of dietary diphenyl diselenide (1ppm) on N-nitroso-N-methylurea (NMU)-induced mammary carcinogenesis was examined in female Wistar rats. Beginning at 5weeks of age, the animals
were fed with either control or diphenyl-diselenide-supplied diets until the end of the study (210days). At 50days of age,
mammary tumor was induced by the administration of three doses of NMU (50mg/kg body wt, intraperitoneally) once a week for
3weeks. In experimental trials, latency to tumor onset was extended in rats fed with diet supplemented with diphenyl diselenide
(P<0.05). The incidence and frequency of tumors were significantly small in animals supplemented with diphenyl diselenide.
However, the multiplicity of tumors was not altered by dietary diphenyl diselenide. Diphenyl diselenide supplementation also
restored superoxide dismutase (SOD) activity and vitamin C levels altered in the NMU group (P<0.05). Our results suggest that diphenyl diselenide can be considered a chemopreventive agent, even when supplemented at
a relatively low concentration.
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ABSTRACT: Mercury is an environmental poison, and the damage to living system is generally severe. The severity of mercury poisoning is consequent from the fact that it targets the thiol-containing enzymes, irreversibly oxidizing their critical thiol groups, consequently leading to an inactivation of the enzyme. The Na⁺/K⁺-ATPase is a sulfhydryl protein that is sensitive to Hg²⁺ assault. On the other hand, organoseleniums are a class of pharmacologically promising compounds with potent antioxidant effects. While Hg²⁺ oxidizes sulfhydryl groups of Na⁺/K⁺-ATPase under in vitro and in vivo conditions, the organoselenium compounds inhibit Na⁺/K⁺-ATPase in vitro but enhance its activities under in vivo conditions with concomitant increase in the level of endogenous thiols. Paradoxically, it appears that these two thiol oxidants can be used to counteract one another under in vivo conditions, and this hypothesis serves as the basis for this paper.Journal of Biomedicine and Biotechnology 01/2012; 2012:924549. · 2.44 Impact Factor
Article: Synthesis and pharmacological screening of several aroyl and heteroaroyl selenylacetic acid derivatives as cytotoxic and antiproliferative agents.[show abstract] [hide abstract]
ABSTRACT: The synthesis and cytotoxic activity of a series of twenty six aroyl and heteroaroyl selenylacetic acid derivatives of general formula Ar-CO-Se-CH(2)-COOH or Heterar-CO-Se-CH(2)-COOH are reported. The synthesis was carried out by reaction of acyl chlorides with sodium hydrogen selenide, prepared in situ, and this led to the formation of sodium aroylselenides that subsequently reacted with alpha-bromoacetic acid to produce the corresponding selenylacetic acid derivatives. All of the compounds were tested against a prostate cancer cell line (PC-3) and some of the more active compounds were assessed against a panel of four human cancer cell lines (CCRF-CEM, HTB-54, HT-29, MCF-7) and one mammary gland-derived non-malignant cell line (184B5). Some of the compounds exhibited remarkable cytotoxic and antiproliferative activities against MCF-7 and PC-3 that were higher than those of the reference compounds doxorubicin and etoposide, respectively. For example, in MCF-7 when Ar = phenyl, 3,5-dimethoxyphenyl or benzyl the TGI values were 3.69, 4.18 and 6.19 microM. On the other hand, in PC-3 these compounds showed values of 6.8, 4.0 and 2.9 microM. Furthermore, benzoylselenylacetic acid did not provoke apoptosis nor did it perturb the cell cycle in MCF-7.Molecules 01/2009; 14(9):3313-38. · 2.39 Impact Factor
Article: High Expression of Cyclin D1 and p21 in N-Nitroso-N-Methylurea-Induced Breast Cancer in Wistar Albino Female Rats.[show abstract] [hide abstract]
ABSTRACT: N-nitroso-N-methylurea (NMU) induces breast cancer in rodents, particularly in rats. This model of breast cancer is very similar to human breast cancer. As a continuation of our recent work, we investigated the expressions of cyclin D1 and p21 in NMU-induced breast cancer of Wistar Albino rats. In this experimental study, mammary carcinoma was induced in female Wistar Albino rats by a new protocol which included the intraperitoneal injection of NMU (50 mg/kg) at 50, 65, and 80 days of the animal's age. The animals were weighed weekly and palpated in order to record the numbers, location, and size of tumors. Subsequently tumor incidence (TI), latency period (LP), and tumor multiplicity (TM) were reported. About four weeks after the tumor size reached 1.5 cm3, rats were sacrificed. Cyclin D1 and p21 expressions in tumors and normal mammary glands from normal rats were measured by reverse-transcription polymerase chain reaction (RT- PCR) and Western blot analysis. Statistical analysis of the data was performed using SPSS software version 16.0. The efficiency of tumor induction was 65%, LP was 150 days, and a TM of 1.43 ± 0.53 per rat was noted. RT-PCR and Western blot data indicated significant (p<0.05) induction of both cyclin D1 and p21 expressions in rat mammary tumors compared with normal tissue from the control group. These results indicate an efficient mammary tumor induction protocol for this type of rat, which is accompanied by an increase in cyclin D1 and p21 expressions.Cell Journal 01/2012; 14(3):193-202.