Oxocrebanine: A Novel Dual Topoisomerase inhibitor, Suppressed the Proliferation of Breast Cancer Cells MCF-7 by Inducing DNA Damage and Mitotic Arrest.

摘要: Abstract Background DNA topoisomerase (Topo) inhibition plays key role in breast cancer treatment. Stephania hainanensis H. S. Lo et Y. Tsoong (S. hainanensis), a Li nationality plant that has abundant aporphine alkaloids, can inhibit Topo. Purpose To identify dual Topo inhibitor, deep and systematic study of active alkaloids their mechanisms inhibiting proliferation activity are essential. Study design This aimed to assess the anti-breast inhibitory activities oxocrebanine explore underlying mechanisms. Methods The growth 12 compounds were screened by MTT assay MCF-7, SGC-7901, HepG-2 cells, compared with effects on human normal mammary epithelial MCF-10A cells as non control cells. was assessed relaxation unwinding assays, kDNA decatenation western blot. Cell cycle autophagy analyses carried out flow cytometry staining. Acridine orange staining α-tubulin morphology observed fluorescence microscopy. Western blot used examine microtubule assembly dynamics expression levels proteins associated damage, mitotic arrest. Results Oxocrebanine alkaloid hainanensis. It exhibited best effect MCF-7 an IC50 16.66 μmol/l, had only weak inhibited I II α cell-free system suggested intercalated catalytic inhibitor. regulated IIα damage-related proteins. led arrest, these occurred through both p53-dependent p53-independent pathways. induced autophagy, abnormal stimulated enhanced dynamics. Conclusion I/IIα inhibitor intercalator. caused arrest also disrupted tubulin polymerization. Accordingly, held great potential for development novel effective