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Berbamine exhibits potent antitumor effects on imatinib-resistant CML cells in vitro and in vivo

  
@article{APS6614,
	author = {Yan-lin Wei and Lei Xu and Yun Liang and Xiao-hua Xu and Xiao-ying Zhao},
	title = {Berbamine exhibits potent antitumor effects on imatinib-resistant CML cells in vitro and in vivo},
	journal = {Acta Pharmacologica Sinica},
	volume = {30},
	number = {4},
	year = {2016},
	keywords = {},
	abstract = {Aim:  The aim of this study was to explore the effects and mechanism of berbamine on imatinib-resistant BCR-ABL-positive human leukemia K562 (K562-r) cells in vitro and in vivo. 
Methods:  Cell viability was measured by MTT assay, and apoptotic morphology changes were detected by fluorescence microscopy. The apoptosis rate was measured by flow cytometric assay. mdr-1 mRNA levels were determined by RT-PCR. Bcl-2 family proteins, cytochrome c(cyt C), poly (ADP-ribose) polymerase (PARP), and P-glycoprotein were detected by Western blot. BALB/c nu/nu mice were injected with K562-r cells subcutaneously. Tumor-bearing mice were treated intravenously with berbamine.
Results:  MTT tests revealed that berbamine significantly inhibited K562-r cell proliferation and increased the chemo-sensitivity of K562-r cells to imatinib. The apoptosis rate was significantly increased following treatment with 21.2 μmol/L berbamine; formation of typical apoptotic blebs was apparent, as observed by fluorescence microscopy. Expression levels of mdr-1 mRNA and P-gp protein were high in untreated K562-r cells and significantly down-regulated by berbamine treatment. Berbamine-treated K562-r cells also exhibited down-regulated expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, up-regulated expression of the apoptotic proteins Bax and cytoplasmic cyt C, and stimulated proteolytic cleavage of PARP. In addition, berbamine also suppressed the growth of K562-r xenotransplanted tumors in vivo. 
Conclusion:  Berbamine inhibited proliferation of K562-r cells both in vitro and in vivo.  Berbamine-induced apoptosis in K562-r cells appeared to occur through a mechanism involving Bcl-2 family proteins, as well as mdr-1 mRNA and P-gp protein. Berbamine in combination with imatinib restored the chemo-sensitivity of K562-r cells to imatinib. Our findings suggest that berbamine may be useful in treating imatinib-resistant CML patients.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/6614}
}