Bersavine is the new bisbenzylisoquinoline alkaloid isolated from the Berberis vulgaris L.(Berberidaceae) plant. The results of cytotoxicity screening 48 h post-treatment showed thatbersavine considerably inhibits the proliferation and viability of leukemic (Jurkat, MOLT-4), colon(HT-29), cervix (HeLa) and breast (MCF-7) cancer cells with IC50 values ranging from 8.1 to 11 μM.The viability and proliferation of leukemic Jurkat and MOLT-4 cells were decreased after bersavinetreatment in a time- and dose-dependent manner. Bersavine manifested concentration-dependentantiproliferative activity in human lung, breast, ovarian and hepatocellular carcinoma cell linesusing a xCELLigence assay. Significantly higher percentages of MOLT-4 cells exposed to bersavineat 20 μM for 24 h were arrested in the G1 phase of the cell cycle using the flow cytometry method.The higher percentage of apoptotic cells was measured after 24 h of bersavine treatment. Theupregulation of p53 phosphorylated on Ser392 was detected during the progression of MOLT-4 cellapoptosis. Mechanistically, bersavine-induced apoptosis is an effect of increased activity ofcaspases, while reduced proliferation seems dependent on increased Chk1 Ser345 phosphorylationand decreased Rb Ser807/811 phosphorylation in human leukemic cells.

ADINACO Research Group Department of Pharmaceutical Botany Faculty of Pharmacy Charles University Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

Department of Biological and Biochemical Sciences Faculty of Chemical Technology University ofPardubice Studentska 573 532 10 Pardubice Czech Republic

Department of Medical Biochemistry Faculty of Medicine in Hradec Kralove Charles University Simkova 870 500 03 Hradec Kralove Czech Republic

Zobrazit více v PubMed

Newman D.J. Natural products as leads to potential drugs: An old process or the new hope for drug discovery? J. Med. Chem. 2008;51:2589–2599. doi: 10.1021/jm0704090. PubMed DOI

Howes M.R. The evolution of anticancer drug discovery from plants. Lancet Oncol. 2018;19:293–294. doi: 10.1016/S1470-2045(18)30136-0. PubMed DOI

Qing Z.X., Huang J.L., Yang X.Y., Liu J.H., Cao H.L., Xiang F., Cheng P., Zeng J.G. Anticancer and Reversing Multidrug Resistance Activities of Natural Isoquinoline Alkaloids and their Structure-activity Relationship. Curr. Med. Chem. 2018;25:5088–5114. doi: 10.2174/0929867324666170920125135. PubMed DOI

Silva Teles M.M.R., Vieira PPinheiro A.A., Da Sliva Dias C., Fechine Tavares J., Barbosa Filho J.M., Leitão Da Cunha E.V. Alkaloids of the Lauraceae. Alkaloids Chem Biol. 2019;82:147–304. PubMed

Hostalkova A., Marikova J., Opletal L., Korabecny J., Hulcova D., Kunes J., Novakova L., Perez D.I., Jun D., Kucera T. Isoquinoline Alkaloids from Berberis vulgaris as Potential Lead Compounds for the Treatment of Alzheimer’s Disease. J. Nat. Prod. 2019;82:239–248. doi: 10.1021/acs.jnatprod.8b00592. PubMed DOI

Liang Y., Qiu X., Xu R.Z., Zhao X.Y. Berbamine inhibits proliferation and induces apoptosis of KU812 cells by increasing Smad3 activity. J. Zhejiang Univ. Sc. B. 2011;12:568–574. doi: 10.1631/jzus.B1000230. PubMed DOI PMC

Jia F., Ruan S., Liu N., Fu L. Synergistic Antitumor Effects of Berbamine and Paclitaxel through ROS/Akt Pathway in Glioma Cells. Evid. Based Compl. Alt. 2017:8152526. doi: 10.1155/2017/8152526. PubMed DOI PMC

Hou Z.B., Lu K.J., Wu X.L., Chen C., Huang X.E., Yin H.T. In vitro and in vivo antitumor evaluation of berbamine for lung cancer treatment. Asian Pac. J. Cancer P. 2014;15:1767–1769. doi: 10.7314/APJCP.2014.15.4.1767. PubMed DOI

Jin X., Wu Y. Berbamine enhances the antineoplastic activity of gemcitabine in pancreatic cancer cells by activating transforming growth factor-beta/Smad signaling. Anat. Rec. 2014;297:802–809. doi: 10.1002/ar.22897. PubMed DOI

Liang Y., Xu R.Z., Zhang L., Zhao X.Y. Berbamine, a novel nuclear factor kappaB inhibitor, inhibits growth and induces apoptosis in human myeloma cells. Acta Pharm. Sin. 2009;30:1659–1665. doi: 10.1038/aps.2009.167. PubMed DOI PMC

Wang G.Y., Lv Q.H., Dong Q., Xu R.Z., Dong Q.H. Berbamine induces Fas-mediated apoptosis in human hepatocellular carcinoma HepG2 cells and inhibits its tumor growth in nude mice. J. Asian Nat. Prod. Res. 2009;11:219–228. doi: 10.1080/10286020802675076. PubMed DOI

Zhao Y., Lv J.J., Chen J., Jin X.B., Wang M.W., Su Z.H., Wang L.Y., Zhang H.Y. Berbamine inhibited the growth of prostate cancer cells in vivo and in vitro via triggering intrinsic pathway of apoptosis. Prostate Cancer P.D. 2016;19:358–366. doi: 10.1038/pcan.2016.29. PubMed DOI

Zhu L., Zhang B., Lu X., Shu Y., Liu B. Delivery of paclitaxel and berbamine by polymeric carriers to cure gastric cancer. Oncol. Res. 2013;20:265–274. doi: 10.3727/096504012X13522227232318. PubMed DOI

Zhang H., Jiao Y., Shi C., Song X., Chang Y., Ren Y., Shi X. Berbamine suppresses cell viability and induces apoptosis in colorectal cancer via activating p53-dependent apoptotic signaling pathway. Cytotechnology. 2018;70:321–329. doi: 10.1007/s10616-017-0146-8. PubMed DOI PMC

Parhi P., Suklabaidya S., Kumar Sahoo S. Enhanced anti-metastatic and anti-tumorigenic efficacy of Berbamine loaded lipid nanoparticles in vivo. Sci. Rep. 2017;7:5806. doi: 10.1038/s41598-017-05296-y. PubMed DOI PMC

Wang G.Y., Zhang J.W., Lu Q.H., Xu R.Z., Dong Q.H. Berbamine induces apoptosis in human hepatoma cell line SMMC7721 by loss in mitochondrial transmembrane potential and caspase activation. J. Zhejiang Univ. Sci. B. 2007;8:248–255. doi: 10.1631/jzus.2007.B0248. PubMed DOI PMC

Liang Y., Zhao X.Y., Wei Y.L., Xu R.Z. Berbamine induces apoptosis of multiple myeloma RPMI 8226 cells by activating GADD45/JNK pathway. Zhejiang Da Xue Xue Bao Yi Xue Ban = J. Zhejiang Univ. Med Sci. 2009;38:439–444. PubMed