ArticlePharmacological reports : PR2026
Interactions of ACEA and WIN 55,212-2 mesylate with temozolomide and cisplatin in neuroblastoma and glioblastoma cell lines: an isobolographic analysis.
Article in Pharmacological reports : PR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundGlioblastoma is still the most aggressive primary brain tumor in adults. Recently, several advanced experimental treatment options have been proposed for glioblastoma patients, including the application of cannabinoids as an add-on therapy.
methodsIn the MTT, LDH, and BrdU assays, the anti-proliferative effects of arachidonyl-2'-chloroethylamide (ACEA - a potent selective cannabinoid CB
resultsACEA and WIN 55,212-2 mesylate produced anti-proliferative effects on the tested cell lines. The selectivity index for ACEA ranged from 2.61 to 5.95, and that for WIN 55,212-2 mesylate ranged from 4.32 to 12.85. The combinations of ACEA with cisplatin (at the fixed ratio of 1:1) exerted additive interactions in all the tested cell lines. In contrast, WIN 55,212-2 mesylate, when combined with cisplatin, exerted a synergistic interaction in the CHP-134 cell line (p < 0.05) and additive interactions in the remaining (KELLY, U-87MG, T98G, and C6) cell lines in the MTT test. The combinations of ACEA with temozolomide (at the fixed-ratio of 1:1) exerted antagonistic interactions in two (CHP-134 at p < 0.05; and C6 at p < 0.0001) cell lines and additive interactions in three (KELLY, U-87MG, T98G) cell lines in the MTT assay. In contrast, WIN 55,212-2 mesylate, when combined with temozolomide, produced antagonistic interactions in three (KELLY at p < 0.05; T98G at p < 0.01, and C6 at p < 0.01) cell lines and additive interactions in the remaining (CHP-134 and U-87MG) cell lines in the MTT test. Western blot analysis confirmed that all the tested cell lines (CHP-134, KELLY, U-87MG, T98G, and C6) exposed to ACEA or WIN 55,212-2 mesylate changed the expression of cannabinoid CB
conclusionsWIN 55,212-2 mesylate combined with cisplatin exerted the most desirable synergistic interaction in relation to the anti-proliferative effects in the neuroblastoma (CHP-134) cell line. In contrast, all the antagonistic interactions determined isobolographically for WIN 55,212-2 mesylate in combination with temozolomide in the KELLY, T98G, C6, and those of ACEA with temozolomide in the CHP-134, C6 cell lines in the MTT assay, should not be used clinically, due to the reduction of the anti-viability effects of the tested combinations.
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