Lobarstin Enhances Chemosensitivity in Human Glioblastoma T98G Cells

Abstract

Lobarstin is a metabolite occurring from the Antarctic lichen Stereocaulon alpnum. Human glioblastoma is highly resistant to chemotherapy with temozolomide. Lobarstin was examined for its effect on glioblastoma. Materials and Methods: Temozolomideresistant T98G cells were subjected to toxicity test with temozolomide and/or lobarstin. DNA damage and recovery was assessed by the alkaline comet assay and expression of DNA repair genes was examined by RT-PCR and western blot analysis. Results: Lobarstin alone at 40 μM was toxic against T98G, but had no effect in primary human fibroblasts. Cotreatment of lobarstin with temozolomide yielded enhanced toxicity. Temozolomide-alone or with lobarstin co-treatment gave similar extent of DNA damage. However, the recovery was reduced in co-treated cells. Expression of DNA repair genes, O6-methylguanine-DNA methyltransferase, poly(ADPribose) polymerase 1 and ligase 3 were reduced in lobarstintreated cells. Conclusion: Enhanced sensitivity to temozolomide by lobarstin co-treatment may be attributed to reduced DNA repair.