title: Secalonic acid A reduced colchicine cytotoxicity through suppression of JNK, p38 MAPKs and calcium influx.
abstract: There are few articles about the cytotoxicity evoked by secalonic acid A (SAA) in some tumor cells. It has not yet been reported whether SAA has any action on neurons of the central nervous system. The aim of this study was to investigate the protective effect of SAA against apoptosis of rat cortical neurons induced by colchicine. The protective action of SAA on the cortical neurons treated with colchicine at 1 μM was examined by Hoechst 33258, LDH release and flow cytometry methods. The results from the above tests indicated that SAA at 3 and 10 μM significantly prevented colchicine-induced apoptosis of the cortical neurons. Further studies from Western blot and confocal microscopy experiments showed that the activation of JNK, p38 MAPKs and caspase-3 during neuron apoptosis triggered by 1 μM colchicine could be obviously suppressed by SAA; on the other hand, an increase in the intracellular free Ca(2+) by 1 μM colchicine in the cortical neuron was blocked evidently by SAA. The above results suggested that SAA could antagonize the cytotoxicity of colchicine in the rat cortical neurons, which may be through inhibition of phosphorylation of JNK and p38 MAPKs, calcium influx, and the activation of caspase-3.
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Aifeng
authors.initials: A
authors.lastname: Zhai
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Zhu
authors.forename: Jinting
authors.initials: J
authors.lastname: Liang
authors.forename: Xuelan
authors.initials: X
authors.lastname: Wang
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Lin
authors.forename: Ruzhu
authors.initials: R
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D061945:Caspase Inhibitors; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D003078:Colchicine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005434:Flow Cytometry; D007202:Indicators and Reagents; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D018613:Microscopy, Confocal; D009183:Mycotoxins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D010143:Paecilomyces / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D044004:Xanthones / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D061945:Caspase Inhibitors; D007202:Indicators and Reagents; D009183:Mycotoxins; D044004:Xanthones; C009218:secalonic acid; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003078:Colchicine; D002118:Calcium