PURPOSE: Aplysin, a natural brominate compound from marine organisms, has been demonstrated to exhibit anti-tumor activity, mainly by inducing apoptosis and cell cycle arrest. However, its effect on glioma is still unknown. In this study, we evaluated the effects of aplysin on the malignant properties of glioma cells and its enhancing effect on temozolomide (TMZ) action against drug-resistant glioma cell lines. METHODS: We employed several human glioma cell lines and primary glioma cells to address this issue with multidisciplinary approaches. RESULTS: The combined application of aplysin and TMZ significantly sensitizes glioma cells to TMZ action, compared with TMZ alone. miRNA profile analysis revealed that the abundance of miR-181, an important glioma tumor suppressors believed to enhance TMZ effect, was greatly elevated in aplysin-treated glioma cell lines. The aplysin-induced TMZ sensitivity is dependent on MEK1 in glioma cells. Overexpression of MEK1 was able to abolish the effect of aplysin on glioma cells. CONCLUSIONS: We found that aplysin can enhance the effect of TMZ on glioma cells by increasing miR-181 expression.
PURPOSE:Aplysin, a natural brominate compound from marine organisms, has been demonstrated to exhibit anti-tumor activity, mainly by inducing apoptosis and cell cycle arrest. However, its effect on glioma is still unknown. In this study, we evaluated the effects of aplysin on the malignant properties of glioma cells and its enhancing effect on temozolomide (TMZ) action against drug-resistant glioma cell lines. METHODS: We employed several humanglioma cell lines and primary glioma cells to address this issue with multidisciplinary approaches. RESULTS: The combined application of aplysin and TMZ significantly sensitizes glioma cells to TMZ action, compared with TMZ alone. miRNA profile analysis revealed that the abundance of miR-181, an important glioma tumor suppressors believed to enhance TMZ effect, was greatly elevated in aplysin-treated glioma cell lines. The aplysin-induced TMZ sensitivity is dependent on MEK1 in glioma cells. Overexpression of MEK1 was able to abolish the effect of aplysin on glioma cells. CONCLUSIONS: We found that aplysin can enhance the effect of TMZ on glioma cells by increasing miR-181 expression.
Authors: Sara García-Davis; Karla Leal-López; Carmen A Molina-Torres; Lucio Vera-Cabrera; Ana R Díaz-Marrero; José J Fernández; Pilar Carranza-Rosales; Ezequiel Viveros-Valdez Journal: Mar Drugs Date: 2020-05-30 Impact factor: 5.118