1.The pro-oxidant buthionine sulfoximine (BSO) reduces tumor growth of implanted Lewis lung carcinoma in mice associated with increased protein carbonyl, tubulin abundance, and aminopeptidase activity.
Rodríguez-Gómez I;Carmona-Cortés J;Wangensteen R;Vargas-Tendero P;Banegas I;Quesada A;García-Lora AM;Vargas F Tumour Biol. 2014 Aug;35(8):7799-805. doi: 10.1007/s13277-014-2046-2. Epub 2014 May 11.
This study evaluated the effects of the pro-oxidant buthionine sulfoximine (BSO) and of the interaction between BSO and TETRAC, an antagonist of αvß3 integrin, on tumor development and aminopeptidase (AP) activity in a murine model of implanted Lewis's carcinoma. Male CBA-C57 mice were untreated (controls) or treated with BSO (222 mg/100 mL in drinking water), TETRAC (10 mg/kg/day, i.p.), or BSO + TETRAC. BSO for 28 days and TETRAC were given for the last 20 days. Mice were subcutaneously inoculated with 1 × 10(6) Lewis carcinoma 3LL cells into the dorsum. Study variables were tumor weight (TW); Hb, as index of tumor-mediated angiogenesis; vascular endothelial growth factor (VEGF) protein abundance; protein carbonyl content; α-tubulin abundance; and GluAp, AlaAp, and AspAp activities. BSO produced a major decrease in TW (203 ± 18 mg) with respect to controls (365 ± 26) and a reduction in Hb content. The TETRAC group also showed marked reductions in TW (129 ± 15) and Hb concentration associated with a reduced VEGF content. The BSO + TETRAC group showed a major TW reduction (125 ± 13); although, the difference with the TETRAC group was not significant. BSO treatment increased protein carbonyl and tubulin abundance in comparison to controls.
2.Aqueous extract of Trigonella foenum-graecum L. ameliorates additive urotoxicity of buthionine sulfoximine and cyclophosphamide in mice.
Bhatia K;Kaur M;Atif F;Ali M;Rehman H;Rahman S;Raisuddin S Food Chem Toxicol. 2006 Oct;44(10):1744-50. Epub 2006 Jun 3.
Cyclophosphamide (CP) is a commonly used anti-cancer drug which causes toxicity by its reactive metabolites such as acrolein and phosphoramide mustard. In the present study modulation of toxicity caused by concomitant exposure to CP and l-buthionine-SR-sulfoximine (BSO) by fenugreek (Trigonella foenum-graecum L.) extract was evaluated by measuring lipid peroxidation (LPO) and anti-oxidants in urinary bladder in mice. Fenugreek, a common dietary and medicinal herb, showed protective effect not only on LPO but also on the enzymatic anti-oxidants. CP-treated animals exhibited a significant decrease in the activities of glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GP) and catalase (CAT) when compared to the controls. Level of reduced glutathione (GSH) was also reduced with an increase in LPO in CP-treated animals. BSO treatment depicted an additive toxic effect in CP-treated animals. Pre-treatment of herbal extract restored activities of all the enzymes and thus showed an overall protective effect on additive effect of CP and BSO. Restoration of GSH by extract treatment may play an important role in reversing CP-induced apoptosis and free radical-mediated LPO in urinary bladder.
3.Effects of glutathione depletion by buthionine sulfoximine on radiosensitization by oxygen and misonidazole in vitro.
Shrieve DC;Denekamp J;Minchinton AI Radiat Res. 1985 Jun;102(3):283-94.
Buthionine sulfoximine (BSO) has been used to deplete glutathione (GSH) in V79-379A cells in vitro, and the effect on the efficiency of oxygen and misonidazole (MISO) as radiosensitizers has been determined. Treatment with 50 or 500 microM BSO caused a rapid decline in GSH content to less than 5% of control values after 10 hr of exposure (t1/2 = 1.6 hr). Removal of BSO resulted in a rapid regeneration of GSH after 50 microM BSO, but little regeneration was observed over the subsequent 10-hr period after 500 microM. Treatment with either of these two concentrations of BSO for up to 14 hr did not affect cell growth or viability. Cells irradiated in monolayer on glass had an oxygen enhancement ratio (OER) of 3.1. After 10-14 hr pretreatment with 50 microM BSO, washed cells were radiosensitized by GSH depletion at all oxygen tensions tested. The OER was reduced to 2.6, due to greater radiosensitization of hypoxic cells than aerated ones by GSH depletion. GSH depletion had the effect of shifting the enhancement ratio vs pO2 curve to lower oxygen tensions, making oxygen appear more efficient by a factor of approximately 2, based on the pO2 required to give an OER of 2.0. In similar experiments performed with MISO, an enhancement ratio of 2.