Major Contribution of Caspase-9 to Honokiol-Induced Apoptotic Insults to Human Drug-Resistant Glioblastoma Cells.

摘要: Temozolomide (TMZ)-induced chemoresistance to human glioblastomas is a critical challenge now. Our previous studies showed that honokiol, major bioactive constituent of Magnolia officinalis (Houpo), can kill glioblastoma cells and suppresses growth. This study was further aimed evaluate the effects honokiol on drug-resistant possible mechanisms. The results by data mining in cancer genome atlas (TCGA) database immunohistochemistry displayed expression caspase-9 mRNA protein induced. Human TMZ-resistant U87-MG-R9 were selected prepared from drug-sensitive U87-MG cells. Compared cells, TMZ did not affect viability Interestingly, treatment with suppressed proliferation survival concentration- time-dependent manners. caspase-8 activation, chiefly increased activity Successively, levels cleaved caspase-3 activities caspase-6 TMZ-tolerant augmented following administration. In parallel, triggered DNA fragmentation Accordingly, induced cell apoptosis but necrosis. Fascinatingly, suppressing using its specific inhibitors repressed honokiol-induced fragmentation, apoptosis. Taken together, this has shown roles transducing mitochondria-dependent Thus, may be clinically applied as drug candidate for patients chemoresistance.