L-Buthionine-(S,R)-sulfoximine (L-Butionine sulfoximine) (Synonyms: L-BSO)

L-Buthionine-(S,R)-sulfoximine is a cell-permeable, potent, fast acting and irreversible inhibitor of g-glutamylcysteine synthetase and depletes cellular glutathione levels. The IC50 value of L-Buthionine-(S,R)-sulfoximine on melanoma, breast and ovarian tumor specimens are 1.9 μM, 8.6 μM, and 29 μM, respectively.

L-Buthionine-(S,R)-sulfoximine (BSO: 50 μM) treatment for 48 hr results in a 95% decrease in ZAZ and M14 melanoma cell line GSH levels, and a 60% decrease in GST enzyme activity. GST-π protein and mRNA levels are significantly reduced in both cell lines[1]. L-Buthionine-(S,R)-sulfoximine (BSO) induces oxidative stress in a cell by irreversibly inhibiting g-glutamylcysteine synthetase, an essential enzyme for the synthesis of glutathione (GSH)[2].

The average number of eye-spots (mean±SEM) is 5.36±0.29 (n=46), 7.79±0.45 (n=34) and 8.78±0.61 (n=32) in untreated controls, 2 mM L-Buthionine-(S,R)-sulfoximine (BSO) and 20 mM BSO treated mice, respectively. The 2 mM BSO treatment results in ~30% more eye-spots, and the 20 mM treatment results in 40% more eye-spots compared with untreated mice. It is showed that BSO causes an elevated frequency of DNA deletions during mouse development. BSO treatment reduced GSH concentration in mouse fetuses by 55% and 70% at 2 mM and 20 mM BSO doses, respectively, compared to untreated mice. Co-treatment with 2 mM BSO and 20 mM NAC depleted GSH to a similar extent as 2 mM BSO, consistent with the function of BSO to inhibit the g-GCS enzyme indispensable for GSH synthesis. Like GSH, cysteine levels dropped following BSO treatment[2].

[1]. Fruehauf JP, et al. Selective and synergistic activity of L-S,R-buthionine sulfoximine on malignant melanoma is accompanied by decreased expression of glutathione-S-transferase. Pigment Cell Res. 1997 Aug;10(4):236-49. [2]. Reliene R, et al. Glutathione depletion by buthionine sulfoximine induces DNA deletions in mice. Carcinogenesis. 2006 Feb;27(2):240-4.