Secalonic acid A reduced colchicine cytotoxicity through suppression of JNK, p38 MAPKs and calcium influx

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 Ca2+ 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.

Research highlights▶ Secalonic acid A has a neuroprotective effect in primarily cultured cortical neurons. ▶ Secalonic acid A inhibits JNK and p38 MAPKs activation induced by colchicine in cortical neurons. ▶ Secalonic acid A inhibits caspase-3 activation induced by colchicine in cortical neurons. ▶ Secalonic acid A down-regulates the calcium influx induced by colchicine in cortical neurons.