Neuroprotective activity of 2-amino-1,3,4-thiadiazole derivative 4BrABT--an in vitro study.
4BrABT (2-(4-Bromophenylamino)-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole) is a compound known for its interesting in vitro anticancer profile. 4BrABT inhibited proliferation and motility of several cancer cell lines in concentrations which were not toxic to normal cells. A major problem associated with cancer chemotherapy, but also caused by environmental factors such as pesticides, is neurotoxicity. Therefore, the aim of the presented study was an in vitro evaluation of the neuroprotective activity of this compound. 4BrABT activity (1-100 μM) was tested in cultures of mouse neurons, rat astrocytes and rat oligodendrocytes. A possible protective action of the compound in different neurodegenerative models, as serum deprivation (SD), excitotoxicity (presence of 500 μM glutamate in culture medium), as well as cisplatin toxicity (astroglia--50 μM and oligodendroglia--100 μM) was investigated. Cell viability in the tested cultures was assessed with the use of LDH and MTT methods. Moreover, 4BrABT ability to prevent the cisplatin-induced apoptosis in astrocyte and oligodendrocyte cultures was analysed after Hoechst 33342 fluorostaining. The obtained results indicate that 4BrABT was not toxic to neurons, astrocytes and oligodendrocytes. Moreover, a decrease in the neuronal LDH level was observed, which may suggest the ability of 4BrABT to act as a trophic agent. Furthermore, the protective action of the studied compound was shown in neuronal cultures exposed to neurotoxic conditions (presence of glutamate and trophic stress) and in cisplatin-treated astrocytes and oligodendrocytes. The expression of anticancer and neuroprotective activity raises hopes for the potential use of 4BrABT as a safe anticancer drug, or neuroprotective agent in chemotherapy-associated neurotoxicity.
Department of Medical Biology, Institute of Rural Health, Lublin, Poland.
Małgorzata
M
Juszczak
Katarzyna
K
Walczak
Ewa
E
Langner
Monika
M
Karpińska
Joanna
J
Matysiak
Wojciech
W
Rzeski
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity; D001253:Astrocytes / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D016895:Culture Media, Serum-Free / Q000633:toxicity; D018698:Glutamic Acid / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D009420:Nervous System / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000633:toxicity; D009836:Oligodendroglia / Q000187:drug effects; D051381:Rats; D013830:Thiadiazoles / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016895:Culture Media, Serum-Free; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D013830:Thiadiazoles; D018698:Glutamic Acid; D002945:Cisplatin