Cytotechnology

, Volume 70, Issue 1, pp 321–329 | Cite as

Berbamine suppresses cell viability and induces apoptosis in colorectal cancer via activating p53-dependent apoptotic signaling pathway

  • Heng Zhang
  • Yunping Jiao
  • Chunyang Shi
  • Xiao Song
  • Ying Chang
  • Yong Ren
  • Xiaolin Shi
Original Article

Abstract

Berbamine has been shown to exhibit anti-cancer activities in various types of cancers. The effects of berbamine on colorectal colon cancer (CRC) have not been examined, and the present study aimed to investigate the anti-cancer effects of berbamine in CRC and explore its underlying molecular mechanisms. The effect of berbamine on the CRC cells was determined by MTT assay. Flow cytometry was performed to examine the effect of berbamine on cell apoptosis and cell cycle as well as mitochondrial membrane potential in CRC cell lines. The specific apoptosis-related factors were evaluated by western blot assay. In vivo anti-cancer effect of berbamine was assessed in SW480 xenografts. Berbamine suppressed the cell viability of CRC cells in concentration-dependent and time-dependent manners. Flow cytometry experiments showed that berbamine increased cell apoptotic rate and induced cell cycle arrest at G0/G1 phase. Berbamine treatment also decreased the mitochondrial membrane potential in CRC cells. Western blot assay showed that berbamine increased the protein levels of p53, caspase-3, caspase-9, Bax and poly ADP ribose polymerase, and decreased the protein levels of Bcl-2 in CRC cells. Berbamine failed to increase the cell apoptotic rate in p53 mutant CRC cell lines. Tumor growth by grafted SW480 cells were significantly suppressed in berbamine group. Expression of p53, caspase-3 and -9 in tumor tissues was significantly up-regulated by berbamine. Berbamine exerts anti-cancer effects in vitro and in vivo via induction of apoptosis, partially associated with the activation of p53-dependent apoptosis signaling pathway.

Keywords

Berbamine Colorectal cancer Cell viability Apoptosis Cell cycle p53 

Notes

Acknowledgements

This work was supported by the Research and Development Project for Science and Technology of Shaanxi Province (Project No. 2013SF2-14).

References

  1. Afshar-Kharghan V (2017) The role of the complement system in cancer. J Clin Invest 127:780–789CrossRefGoogle Scholar
  2. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66:683–691CrossRefGoogle Scholar
  3. Aung TN, Qu Z, Kortschak RD, Adelson DL (2017) Understanding the effectiveness of natural compound mixtures in cancer through their molecular mode of action. Int J Mol Sci 18:656CrossRefGoogle Scholar
  4. Bernabeu E, Cagel M, Lagomarsino E, Moretton M, Chiappetta DA (2017) Paclitaxel: what has been done and the challenges remain ahead. Int J Pharm 526:474–495CrossRefGoogle Scholar
  5. Chen L, Jiang J, Cheng C, Yang A, He Q, Li D et al (2007) P53 dependent and independent apoptosis induced by lidamycin in human colorectal cancer cells. Cancer Biol Ther 6:965–973CrossRefGoogle Scholar
  6. Corona SP, Ravelli A, Cretella D, Cappelletti MR, Zanotti L, Dester M et al (2017) CDK4/6 inhibitors in HER2-positive breast cancer. Crit Rev Oncol Hematol 112:208–214CrossRefGoogle Scholar
  7. Duan H, Luan J, Liu Q, Yagasaki K, Zhang G (2010) Suppression of human lung cancer cell growth and migration by berbamine. Cytotechnology 62:341–348CrossRefGoogle Scholar
  8. Frouws MA, van Herk-Sukel MP, Maas HA, Van de Velde CJ, Portielje JE, Liefers GJ et al (2017) The mortality reducing effect of aspirin in colorectal cancer patients: interpreting the evidence. Cancer Treat Rev 55:120–127CrossRefGoogle Scholar
  9. Gill S, Thomas RR, Goldberg RM (2003) Review article: colorectal cancer chemotherapy. Aliment Pharmacol Ther 18:683–692CrossRefGoogle Scholar
  10. Greenwell M, Rahman PK (2015) Medicinal plants: their use in anticancer treatment. Int J Pharm Sci Res 6:4103–4112Google Scholar
  11. Hou ZB, Lu KJ, Wu XL, Chen C, Huang XE, Yin HT (2014) In vitro and in vivo antitumor evaluation of berbamine for lung cancer treatment. Asian Pac J Cancer Prev 15:1767–1769CrossRefGoogle Scholar
  12. Jin X, Wu Y (2014) Berbamine enhances the antineoplastic activity of gemcitabine in pancreatic cancer cells by activating transforming growth factor-beta/Smad signaling. Anat Rec (Hoboken) 297:802–809CrossRefGoogle Scholar
  13. Karimian A, Ahmadi Y, Yousefi B (2016) Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage. DNA Repair (Amst) 42:63–71CrossRefGoogle Scholar
  14. Khan I, Qayum A, Qureshi Z (1969) Study of the hypotensive action of berbamine, an alkaloid isolated from berberis lycium. Life Sci 8:993–1001CrossRefGoogle Scholar
  15. Kocab AJ, Duckett CS (2016) Inhibitor of apoptosis proteins as intracellular signaling intermediates. FEBS J 283:221–231CrossRefGoogle Scholar
  16. Lai CY, Tsai AC, Chen MC, Chang LH, Sun HL, Chang YL et al (2012) Aciculatin induces p53-dependent apoptosis via MDM2 depletion in human cancer cells in vitro and in vivo. PLoS ONE 7:e42192CrossRefGoogle Scholar
  17. Liang Y, Xu RZ, Zhang L, Zhao XY (2009) Berbamine, a novel nuclear factor kappaB inhibitor, inhibits growth and induces apoptosis in human myeloma cells. Acta Pharmacol Sin 30:1659–1665CrossRefGoogle Scholar
  18. Liang Y, Qiu X, Xu RZ, Zhao XY (2011) Berbamine inhibits proliferation and induces apoptosis of KU812 cells by increasing Smad3 activity. J Zhejiang Univ Sci B 12:568–574CrossRefGoogle Scholar
  19. Liu W, Li J, Song YS, Li Y, Jia YH, Zhao HD (2017) Cdk5 links with DNA damage response and cancer. Mol Cancer 16:60CrossRefGoogle Scholar
  20. Meng Z, Li T, Ma X, Wang X, Van Ness C, Gan Y et al (2013) Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca(2)(+)/calmodulin-dependent protein kinase II. Mol Cancer Ther 12:2067–2077CrossRefGoogle Scholar
  21. Niknejad H, Yazdanpanah G, Ahmadiani A (2016) Induction of apoptosis, stimulation of cell-cycle arrest and inhibition of angiogenesis make human amnion-derived cells promising sources for cell therapy of cancer. Cell Tissue Res 363:599–608CrossRefGoogle Scholar
  22. Nobili S, Lippi D, Witort E, Donnini M, Bausi L, Mini E et al (2009) Natural compounds for cancer treatment and prevention. Pharmacol Res 59:365–378CrossRefGoogle Scholar
  23. Tan CJ, Zhao Y, Goto M, Hsieh KY, Yang XM, Morris-Natschke SL et al (2016) Alkaloids from Oxytropis ochrocephala and antiproliferative activity of sophoridine derivatives against cancer cell lines. Bioorg Med Chem Lett 26:1495–1497CrossRefGoogle Scholar
  24. Wang GY, Zhang JW, Lu QH, Xu RZ, Dong QH (2007) Berbamine induces apoptosis in human hepatoma cell line SMMC7721 by loss in mitochondrial transmembrane potential and caspase activation. J Zhejiang Univ Sci B 8:248–255CrossRefGoogle Scholar
  25. Wang GY, Lv QH, Dong Q, Xu RZ, Dong QH (2009) Berbamine induces Fas-mediated apoptosis in human hepatocellular carcinoma HepG2 cells and inhibits its tumor growth in nude mice. J Asian Nat Prod Res 11:219–228CrossRefGoogle Scholar
  26. Wong CW, Seow WK, O’Callaghan JW, Thong YH (1992) Comparative effects of tetrandrine and berbamine on subcutaneous air pouch inflammation induced by interleukin-1, tumour necrosis factor and platelet-activating factor. Agents Actions 36:112–118CrossRefGoogle Scholar
  27. Yang F, Nam S, Zhao R, Tian Y, Liu L, Horne DA et al (2013) A novel synthetic derivative of the natural product berbamine inhibits cell viability and induces apoptosis of human osteosarcoma cells, associated with activation of JNK/AP-1 signaling. Cancer Biol Ther 14:1024–1031CrossRefGoogle Scholar
  28. Zhang CM, Gao L, Zheng YJ, Yang HT (2012) Berbamine protects the heart from ischemia/reperfusion injury by maintaining cytosolic Ca(2+) homeostasis and preventing calpain activation. Circ J 76:1993–2002CrossRefGoogle Scholar
  29. Zhao Y, Lv JJ, Chen J, Jin XB, Wang MW, Su ZH et al (2016) Berbamine inhibited the growth of prostate cancer cells in vivo and in vitro via triggering intrinsic pathway of apoptosis. Prostate Cancer Prostatic Dis 19:358–366CrossRefGoogle Scholar
  30. Zhu L, Zhang B, Lu X, Shu Y, Liu B (2013) Delivery of paclitaxel and berbamine by polymeric carriers to cure gastric cancer. Oncol Res 20:265–274CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Heng Zhang
    • 1
  • Yunping Jiao
    • 2
  • Chunyang Shi
    • 3
  • Xiao Song
    • 1
  • Ying Chang
    • 1
  • Yong Ren
    • 4
  • Xiaolin Shi
    • 1
  1. 1.Department of Pharmacythe Northwest Women and Children’s HospitalXi’anChina
  2. 2.Department of PharmacyShaanxi No. 2 People’s HospitalXi’anChina
  3. 3.School of Food and Biological EngineeringShaanxi University of Science and TechnologyXi’anChina
  4. 4.Department of Pharmacythe First Affiliated Hospital of Xi’an Medical UniversityXi’anChina

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