BACKGROUND/AIM: 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: Temozolomide-resistant 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. Co-treatment 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, O(6)-methylguanine-DNA methyltransferase, poly(ADP-ribose) polymerase 1 and ligase 3 were reduced in lobarstin-treated cells. CONCLUSION: Enhanced sensitivity to temozolomide by lobarstin co-treatment may be attributed to reduced DNA repair.
BACKGROUND/AIM: Lobarstin is a metabolite occurring from the Antarctic lichen Stereocaulon alpnum. Humanglioblastoma is highly resistant to chemotherapy with temozolomide. Lobarstin was examined for its effect on glioblastoma. MATERIALS AND METHODS:Temozolomide-resistant 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. Co-treatment 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, O(6)-methylguanine-DNA methyltransferase, poly(ADP-ribose) polymerase 1 and ligase 3 were reduced in lobarstin-treated cells. CONCLUSION: Enhanced sensitivity to temozolomide by lobarstin co-treatment may be attributed to reduced DNA repair.
Entities:
Keywords:
DNA repair; Lobarstin; chemosensitivity; glioblastoma; temozolomide
Authors: Martina Da Ros; Veronica De Gregorio; Anna Lisa Iorio; Laura Giunti; Milena Guidi; Maurizio de Martino; Lorenzo Genitori; Iacopo Sardi Journal: Int J Mol Sci Date: 2018-09-22 Impact factor: 5.923
Authors: Elżbieta Studzińska-Sroka; Aleksandra Majchrzak-Celińska; Przemysław Zalewski; Dominik Szwajgier; Ewa Baranowska-Wójcik; Barbara Kaproń; Tomasz Plech; Marcin Żarowski; Judyta Cielecka-Piontek Journal: Pharmaceuticals (Basel) Date: 2021-12-10