5-Demethylnobiletin promotes the formation of polymerized tubulin, leads to G2/M phase arrest and induces autophagy via JNK activation in human lung cancer cells

摘要: 5-Demethylnobiletin is a hydroxylated polymethoxyflavone found in citrus plants that shows antiproliferative activities several cancer cell lines. In this study, we investigated the effects and underlying molecular mechanisms of 5-demethylnobiletin on inhibition growth, apoptosis, cycle autophagy A549 CL1-5 lung cells. The results 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay suggested inhibited growth dose- time-dependent manner. Flow cytometry proliferation cells by inducing G2/M phase arrest but predominantly not through apoptosis. Western blot illustrated blockade was associated with reduced levels cdc25 cdc2. Notably, our indicated induced significant abnormal microtubule dynamics cells, novel finding. Studies conducted isolated tubulin docking models suggest promoted polymerization microtubules bound to taxol site. Additionally, might also induce via activation JNK signaling pathway Pretreatment inhibitor 3-methyladenine significantly potentiated 5-demethylnobiletin-induced suggesting mitigated Further investigation revealed reproducible nude mouse model. Taken together, these studies has anti-lung efficacy both vitro vivo possibly induction arrest,