title: Antidepressant drugs can modify cytotoxic action of temozolomide.
abstract: Cancer patients often require antidepressant treatment due to comorbid depressive disorder. However, recent studies have demonstrated that antidepressant drugs affect the efficacy of chemotherapy and promote progression of cancer. Apart from the main mood-improving effect, antidepressant drugs also produce analgesic, anxiolytic, hypnotic and pro-cognitive actions. Patients suffering from brain cancer constitute the greatest percentage of depressive cancer patients. However, vital safety and efficacy issues related to combined therapy with temozolomide, the first-line cytostatic in patients diagnosed with glioblastoma multiforme, and antidepressant drugs have yet to be addressed. The aim of the present studies was to evaluate the effect of three antidepressant drugs (imipramine, fluoxetine and tranylcypromine) on the cytotoxic efficacy of temozolomide on T98G cells, a human glioblastoma cell line. In our experiments, we used a complex experimental in vitro system to mimic the instability of a tumour's oxygen supply, thereby reproducing conditions that occur inside the tumour. The effect of the interaction between temozolomide and antidepressant drugs on viability, apoptosis and intensity of divisions of glioblastoma cells was evaluated under different oxygen conditions. The results of our studies demonstrated that imipramine and tranylcypromine reduced the cytotoxic efficacy of temozolomide under some oxygen conditions while fluoxetine did not demonstrate such effects.
authors.affiliation: Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: A M
authors.initials: AM
authors.lastname: Bielecka
authors.affiliation: Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Obuchowicz
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000523:psychology; D004347:Drug Interactions; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy / Q000523:psychology; D006801:Humans; D007099:Imipramine / Q000494:pharmacology* / Q000627:therapeutic use; D000077204:Temozolomide; D014191:Tranylcypromine / Q000494:pharmacology* / Q000627:therapeutic use; D000072258:Tumor Hypoxia
chemical_list: D000928:Antidepressive Agents; D018906:Antineoplastic Agents, Alkylating; D005473:Fluoxetine; D014191:Tranylcypromine; D003606:Dacarbazine; D007099:Imipramine; D000077204:Temozolomide
keywords: adjuvant therapy in brain cancer; chemobrain; depression in brain cancer; glioblastoma multiforme treatment; pharmacological interactions in cancer treatment