Methylseleninic acid, a potent growth inhibitor of synchronized mouse mammary epithelial tumor cells in vitro

Sinha, Raghu; Unni, Emmanual; Ganther, Howard E.; Medina, Daniel

doi:10.1016/s0006-2952(00)00545-1

Cited by 54 publications

(45 citation statements)

References 21 publications

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“…Sinha et al reported that MSA at a low concentration (5×10 −6 mol/L) inhibited the growth of the mouse mammary epithelial tumor cell line, TM6 at the G 1 phase, whereas a high concentration (5×10 −5 mol/L) could induce apoptosis. 21) Another study showed that 5×10 −6 mol/L MSA inhibited the growth of MCF10AT1 and MCF10AT3B premalignant human breast cells, and a high concentration could induce apoptosis. 22) Our results indicated that a concentration of 2.5×10 −6 mol/L MSA may be sufficient for the G 1 arrest and induction of apoptosis in A549 cells.…”

Section: Discussionmentioning

confidence: 99%

Glutathione-Dependent Cell Cycle G<sub>1</sub> Arrest and Apoptosis Induction in Human Lung Cancer A549 Cells Caused by Methylseleninic Acid: Comparison with Sodium Selenite

Okuno

Honda

Arakawa

et al. 2014

Biological & Pharmaceutical Bulletin

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The aim of the present study was to clarify the mechanism underlying the inhibition of cell proliferation in human lung cancer A549 cells by selenium (Se) compounds. Methylseleninic acid (CH 3 SeO 2 H, abbreviated as MSA), a synthetic Se compound, is a direct precursor of active methylselenol (CH 3 SeH) and is considered to be one of beneficial agents for cancer prevention and therapy. Sodium selenite (Na 2 SeO 3 ), an inorganic Se form, is utilized in clinical Se supplementation. MSA markedly inhibited the growth of A549 cells at a concentration of 2.5 10 6 mol/L for 1 d. On Day 1, Na 2 SeO 3 also inhibited A549 cell growth at the concentration of 7.5 10 6 mol/L. These compounds induced cell cycle arrest at the G 1 phase and apoptosis under the inhibitory condition. Reduced glutathione (GSH) is critical to MSA or Na 2 SeO 3 metabolism. The depletion of intracellular GSH suppressed Na 2 SeO 3 -induced G 1 arrest, but promoted Na 2 SeO 3 -induced apoptosis. Therefore, Na 2 SeO 3 appears to have directly induced apoptosis. In contrast, the MSA-induced G 1 arrest was ameliorated by a marked decrease in GSH content. Additionally, the depletion of GSH slightly suppressed MSA-induced apoptosis. The difference in inhibitory effects between MSA and Na 2 SeO 3 may be due to this variation in GSH-related metabolism. After exposure of A549 cells to MSA, the GSH content was significantly decreased. These results indicate that because MSA-induced G 1 arrest and apoptosis induction are enhanced by GSH, the maintenance of GSH is essential for the effective anticancer action of MSA in A549 cells.

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Section: Discussionmentioning

confidence: 99%

Glutathione-Dependent Cell Cycle G<sub>1</sub> Arrest and Apoptosis Induction in Human Lung Cancer A549 Cells Caused by Methylseleninic Acid: Comparison with Sodium Selenite

Okuno

Honda

Arakawa

et al. 2014

Biological & Pharmaceutical Bulletin

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“…When cells reached ϳ40 -60% confluence, the medium was changed, and 12-24 h later the cells were treated with 3, 10, or 30 M MSA (pH adjusted to 7.0) (Selenium Technologies, Lubbock, TX). The doses used in this study were chosen based on previous studies using MSA in vitro and reported selenium levels in human serum (Ip et al, 2000b;Nomura et al, 2000;Brooks et al, 2001a;Jiang et al, 2001;Sinha et al, 2001;Dong et al, 2002;Zhu et al, 2002). At several time points after exposure, total RNA was harvested as described below.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Diverse Effects of Methylseleninic Acid on the Transcriptional Program of Human Prostate Cancer Cells

Zhao

Whitfield

et al. 2004

MBoC

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Methylseleninic acid (MSA) has been shown to have potent anticancer activity and is an excellent compound for studying the anticancer effects of selenium in vitro. To gain insights into the effects of MSA in prostate cancer, we characterized the global transcriptional response of LNCaP, an androgen-sensitive human prostate cancer cell line, to MSA by using high-density cDNA microarrays. We identified 951 genes whose expression shows striking dose-and time-dependent changes in response to 3-30 M MSA over the time course of 48 h. Transcript levels of many cell cycle-regulated genes change in response to MSA, suggesting that MSA inhibits proliferation. Consistent with these gene expression changes, cell proliferation, monitored by carboxyfluoroscein succinimidyl ester staining, was decreased after MSA treatment, and an accumulation of cells at G0/G1 phase was detected by flow cytometry. Surprisingly, MSA also modulated expression of many androgen-regulated genes, suppressed androgen receptor (AR) expression at both mRNA and protein level, and decreased levels of prostate specific antigen secreted into the medium. Low concentrations of MSA also induced significant increases in transcript levels of phase 2 detoxification enzymes and induced NADPH dehydrogenase, quinone 1 enzymatic activity, a surrogate marker of global phase 2 enzyme activity. Our results suggest that MSA may protect against prostate cancer by inhibiting cell proliferation, by modulating the expression of AR and AR-regulated genes and by inducing carcinogen defenses.

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“…1,2) These compounds also present other pharmacological properties such as antibacterial, antiviral, anti-fungal, anti-parasitic, antihistamine and anti-inflammatory effects. [3][4][5] Other properties include central nervous system inhibition, anaesthetic, hypnotic, tranquilliser and analgesic activities.…”

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confidence: 99%

Antinociceptive Profile of 2-Phenylselenenyl-1,8-cineole in Mice

Sousa

Raphael

Brocksom

et al. 2004

Biological & Pharmaceutical Bulletin

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Organo-selenium compounds are already known for their anti-cancer activity, being effective against several kind of tumours. 1,2) These compounds also present other pharmacological properties such as antibacterial, antiviral, anti-fungal, anti-parasitic, antihistamine and anti-inflammatory effects. [3][4][5] Other properties include central nervous system inhibition, anaesthetic, hypnotic, tranquilliser and analgesic activities. 5-7)These facts led us to verify in mice the antinociceptive potential of 2-phenylselenenyl-1,8-cineole (PSC), 8,9) an intermediate obtained in our terpene total synthesis studies.10) To our knowledge this is the first study describing the analgesic effects of PSC. MATERIALS AND METHODS ChemicalCompound PSC was prepared in our laboratory as already described, 8) and dissolved in 5% Tween 20 as an emulsion.Animals Male Swiss mice (26-36 g; 6-8 weeks old) were obtained from the Biology Dept. of this University. The animals were maintained at constant room temperature (23Ϯ1°C) and on a 12/12 h light-dark cycle (light from 7:00 to 19:00 h), with free access to food and water and for a minimum of 7 d before performing the experiments. All behavioural observations were conducted between 13:00 and 19:00 h.Statistical Statistical analysis was performed by means of variance analysis followed by Student's t-test or Dunnet's test. A probability level of 0.01 or 0.05 was accepted as significant.Acute Toxicity and Behavioural Effects The toxicity study was performed with different doses of PSC to groups of mice (nϭ10) administered intraperitoneal (i.p.), and mortality was recorded for 72 h for the determination of LD50. 11)According to the method of Irwin, 12) the behaviour of the mice was observed at 1 and 2 h after i.p. injection of PSC.Pentobarbital-Induced Sleeping Time Sodium pentobarbital at a hypnotic dose of 50 mg/kg was injected i.p. to 2 groups (nϭ10) of mice 60 min after pre-treatment with 0.9% saline (control) and PSC (30 mg/kg) i.p., respectively. The duration of sleep time (loss and recovery of the righting reflex) was recorded. 13)Tail Immersion Method The tail (up to 5 cm) of the mice were dipped into a beaker containing water kept at 50°C. The time for the mice to remove its tail from the hot water was recorded and a maximum 60 s cut-off was used. The mice were divided into 3 groups (nϭ10). Saline 0.9% (control), PSC (30 mg/kg) and morphine (6 mg/kg) were administered i.p. Readings were taken at 60, 120, 180 and 240 min after drug injection. 14)Acetic Acid Induced Writhing The mice were divided into 6 groups (nϭ10) and pre-treated with saline 0.9% (control). PSC (15, 30, 60 mg/kg), 1,8-cineole (150 mg/kg) and morphine (6 mg/kg) were administered i.p. After 60 min an acetic acid solution (0.6%; 0.1 ml/10 g) was i.p. injected. After a further 5 min, the number of constrictions was recorded for 5 min. 15) RESULTS AND DISCUSSIONIn this work, the effects of PSC were evaluated for central pharmacological activity. PSC did not induce mortality up to a dose of 120 mg/kg in mice. On the basis...

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Methylseleninic acid, a potent growth inhibitor of synchronized mouse mammary epithelial tumor cells in vitro

Cited by 54 publications

References 21 publications

Glutathione-Dependent Cell Cycle G<sub>1</sub> Arrest and Apoptosis Induction in Human Lung Cancer A549 Cells Caused by Methylseleninic Acid: Comparison with Sodium Selenite

Glutathione-Dependent Cell Cycle G<sub>1</sub> Arrest and Apoptosis Induction in Human Lung Cancer A549 Cells Caused by Methylseleninic Acid: Comparison with Sodium Selenite

Diverse Effects of Methylseleninic Acid on the Transcriptional Program of Human Prostate Cancer Cells

Antinociceptive Profile of 2-Phenylselenenyl-1,8-cineole in Mice

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