Berberine Berberine is an isoquinoline alkaloid isolated from Coptidis Rhizoma, and that is a Chinese medicinal herb for heat dissipation and detoxification, with its dry herb bodyweight consisting of up to 7. 1 mg/100 mg of berberine. Berberine has various pharmacolo gical activities and is particularly made use of as an anti bacterial and anti inflammatory gastrointestinal remedy in China. Berberine has anti proliferative effects on cancer cells continues to be documented. Several tar will get of berberine have already been recognized, which includes mito chondria, DNA or RNA, DNA topoisomerases, estrogen receptors, MMPs, p53 and NF B. Berberine exerts cytotoxicity and inhibits telomerase and topoi somerase in cancer cells by exclusively binding to oligo nucleotides or polymorphic nucleic acid and by stabilizing DNA triplexes or G quadruplexes, the electrostatic interactions may well be quantified with regards to the Hill model of cooperative interactions.
Cell cycle regulation is actually a prevalent target mechanism in anti cancer therapies. A minimal selelck kinase inhibitor dose ber berine therapy induces G1 phase arrest whereas doses larger than 50 uM induce G2 phase arrest in mouse melanoma K1735 M2 and human melanoma WM793 cells. Also, 50 uM berberine decreases cyclin B1 ranges and induces cycle arrest on the G1 phase in human lung cancer H1299 and A549 cell lines. Even in anoikis resistant human breast cancer MDA MB 231 and MCF 7 cells, 10 or twenty uM doses of berber ine is superior to five or 10 nM of doxorubicine respec tively by inducing cell cycle arrest in the G0/G1 phase.
In human breast cancer MCF 7 cells, berberine induces apoptosis MEK ic50 by means of a mitochondrial dependent pathway by growing the Bcl 2 linked ? protein /Bcl two protein ratio, activating caspases and indu cing poly polymerase cleavage. These apoptotic processes also take place in human tongue squamous carcinoma cancer 4 and human glio blastoma T98G cells. Accumulation of berberine on mitochondrial membranes alters the binding involving adenine nucleotide translocator and bongkrekic acid, therefore inducing depolarization and fragmentation which may contribute to mitochondrial respiration inhi bition and mitochondrial dysfunction. While in the p53 expressing human neuroblastoma SK N SH and p53 deficient SK N MC cells, the role of p53 in berberines anti neoplastic function is highlighted by the cytotoxic effects and apoptotic gene expression accompanied by caspase 3 activation.
As well as apoptotic alteration induced by berber ine, recent findings are about anti cancer mechanisms that have a higher propensity to result in autophagy. Berber ine induces autophagic cell death in human hepatocellu lar liver carcinoma cell lines and MHCC97 L cells, which might be diminished by cell death inhibitor three methyladenine via beclin one activation and mamma lian target of rapamycin signaling pathway inhi bition.