Disulfiram sensitizes pituitary adenoma cells to temozolomide by regulating O6-methylguanine-DNA methyltransferase expression

Disulfiram (DSF) reduced MGMT protein expression and sensitized human pituitary adenoma cells to temozolomide (TMZ) both in vitro and in vivo.

• MGMT activity is linked to resistance against TMZ in aggressive pituitary adenomas.
• DSF has been shown to induce loss of MGMT protein, enhancing TMZ effectiveness in glioblastoma cells.
• CD133+ nestin+ cells are identified as stem-like cells within pituitary adenomas.
• In vitro experiments demonstrated that DSF sensitized both human pituitary adenoma cells and their stem-like counterparts to TMZ.
• The proteasome inhibitor PS-341 countered the effect of DSF on MGMT expression in vitro.
• The findings suggest that DSF may enhance the anti-tumor effects of TMZ via the elimination of MGMT protein.

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