Combination efficacy of drugs with antitumor activity against human glioblastoma cells

<p>Glioblastoma is one of the most malignant brain tumors. No effective treatment against glioblastoma has been established. Recently, drug repositioning approaches have identified existing drugs that show antitumor effects against glioblastoma in vitro. In this study, we investigated the combinations of existing drugs with antitumor effects against glioblastoma that show additive and synergistic effects in combination with each other, with the aim of developing more effective therapies for glioblastoma. We examined the effects of arsenite, ascorbic acid (AA), retinol (Rol), retinoic acid (RA), and valproic acid (VPA) alone or in combination on the viability of human glioblastoma U251 cells. As a result, Rol, a vitamin A (VA) derivative, showed an additive effect when combined with VPA and a synergistic effect when combined with RA. In addition, AA [vitamin C (VC)] showed a synergistic antitumor effect when used in combination with arsenite. Both VA and VC have been reported to exhibit antitumor effects via induction of endoplasmic reticulum (ER) stress. The combination of Rol and RA or arsenite and AA increased the expression of ER stress markers (CHOP and GRP78), suggesting that these combinations may exert antitumor effects against glioblastoma via the induction of ER stress.</p>