Skip to main content
SpringerLink
Log in

Berberine-induced changes in protein expression and antioxidant enzymes in melanoma cells

  • Original Paper
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Proteomic identification of differentially expressed proteins after treatment with berberine, a natural alkaloid, was investigated in this study. The 23 differentially expressed proteins, 3 of which were enhanced and 20 were reduced, were associated with diverse biological functions including cell death and molecular chaperone. The proteomic result was also validated by western blot analysis of ezrin, septin, UQCRC1 and elongation factor Tu. Moreover, changes in total activity and isozyme pattern of antioxidant enzymes were examined via activity assay and in-situ activity staining, respectively. Total activities of catalase and superoxide dismutase were enhanced, while those of glutathione peroxidase and glutathione reductase were unchanged by berberine. Taken together, the results showed that berberine elicited alteration of protein expression patterns and signaled the induction of isozyme of catalase and superoxide dismutase in melanoma cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Tang, W. C. & Lee, K. H. Inhibitory effects of berberine on the migratory and invasive abilities of cancer cells. Cancer Cell Microenviron 2:e710 (2015).

    Google Scholar 

  2. Lee, Y. K., Park, S. Y., Kim, Y. M. & Park, O. J. Regulatory effect of the AMPK-COX-2 signaling pathway in curcumin-induced apoptosis in HT-29 colon cancer cells. Ann N Y Acad Sci 1171:489–494 (2009).

    Article  CAS  PubMed  Google Scholar 

  3. Yount, G. et al. Berberine sensitizes human glioma cells, but not normal glial cells, to ionizing radiation in vitro. J Exp Ther Oncol 4:137–143 (2004).

    CAS  PubMed  Google Scholar 

  4. Meeran, S. M., Katiyar, S. & Katiyar, S. K. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation. Toxicol Appl Pharmacol 229:33–43 (2008).

    Article  CAS  PubMed  Google Scholar 

  5. Jhappan, C., Noonan, F. P. & Merlino, G. Ultraviolet radiation and cutaneous malignant melanoma. Oncogene 22:3099–3112 (2003).

    Article  CAS  PubMed  Google Scholar 

  6. Gray-Schopfer, V., Wellbrock, C. & Marais, R. Melanoma biology and new targeted therapy. Nature 445: 851–857 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Chou, H. C. et al. Proteomic and redox-proteomic analysis of berberine-induced cytotoxicity in breast cancer cells. J Proteomics 18:3158–3176 (2012).

    Article  Google Scholar 

  8. Park, S. K., Ryu, A. R. & Lee, M. Y. Protein expression profiling in the liver of rats exposed to phenanthrene. Mol Cell Toxicol 9:267–275 (2013).

    Article  CAS  Google Scholar 

  9. Schuette, J. C. et al. GTPase activation of elongation factor EF-Tu by the ribosome during decoding. EMBO J 28:755–765 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bretscher, A., Reczek, D. & Berryman, M. Ezrin: a protein requiring conformational activation to link micro filaments to the plasma membrane in the assembly of cell surface structures. J Cell Sci 110:3011–3018 (1997).

    CAS  PubMed  Google Scholar 

  11. Rasmussen, M. et al. Osmotic cell shrinkage activates ezrin/radixin/moesin (ERM) proteins: activation mechanisms and physiological implications. Am J Physiol Cell Physiol 294:197–212 (2008).

    Article  Google Scholar 

  12. Hatano, R. et al. Ezrin, a membrane cytoskeletal crosslinker, is essential for the regulation of phosphate and calcium homeostasis. Kidney Int 83:41–49 (2013).

    Article  CAS  PubMed  Google Scholar 

  13. Arpin, M., Chirivino, D., Naba, A. & Zwaenepoel, I. Emerging role for ERM proteins in cell adhesion and migration. Cell Adh Migr 5:199–206 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Akter, R., Rivas, D., Geneau, G., Drissi, H. & Duque, G. Effect of lamin A/C knockdown on osteoblast differentiation and function. J Bone Miner Res 24:283–293 (2009).

    Article  CAS  PubMed  Google Scholar 

  15. Okinaga, T., Kasai, H., Tsujisawa, T. & Nishihara, T. Role of caspases in cleavage of lamin A/C and PARP during apoptosis in macrophages infected with a periodontopathic bacterium. J Med Microbiol 56:1399–1404 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Hara, A. et al. Localization of septin 8 in murine retina, and spatiotemporal expression of septin 8 in a murine model of photoreceptor cell degeneration. Neurosci Lett 423:205–210 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Joo, E., Surka, M. C. & Trimble, W. S. Mammalian SEPT2 is required for scaffolding nonmuscle myosin II and its kinases. Dev Cell 13:677–690 (2007).

    Article  CAS  PubMed  Google Scholar 

  18. Sirajuddin, M., Farkasovsky, M., Zent, E. & Wittinghofer, A. GTP-induced conformational changes in septins and implications for function. Proc Natl Acad Sci U S A 106:16592–16597 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pissuti Damalio, J. C. et al. Self assembly of human septin 2 into amyloid filaments. Biochimie 94:628–636 (2012).

    Article  PubMed  Google Scholar 

  20. Hannon, R. et al. Aberrant inflammation and resistance to glucocorticoids in annexin 1-/-mouse. FASEB J 17:253–255 (2003).

    CAS  PubMed  Google Scholar 

  21. Ang, E. Z., Nguyen, H. T., Sim, H. L., Putti, T. C. & Lim, L. H. Annexin-1 regulates growth arrest induced by high levels of estrogen in MCF-7 breast cancer cells. Mol Cancer Res 7:266–274 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Skop, V. et al. Autophagy inhibition in early but not in later stages prevents 3T3-L1 differentiation Effect on mitochondrial remodeling. Differentiation 87:220–229 (2014).

    Article  CAS  PubMed  Google Scholar 

  23. Liu, C. I. et al. Proteomic analysis of anti-tumor effects of 11-dehydrosinulariolide on CAL-27 cells. Mar Drugs 9:1254–1272 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Xue-hai, L., Wen, S., Hong, S., Thazha, P. P. & Stanley, T. C. TCP1 complex proteins interact with phosphorothioate oligonucleotides and can co-localize in oligonucleotide-induced nuclear bodies in mammalian cells. Nucleic Acids Res 42:7819–7832 (2014).

    Article  Google Scholar 

  25. Balla, G. et al. Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem 267:18148–18153 (1992).

    CAS  PubMed  Google Scholar 

  26. Basu, A. et al. Proteome analysis of the triton-insoluble erythrocyte membrane skeleton. J Proteomics 128: 298–305 (2015).

    Article  CAS  PubMed  Google Scholar 

  27. Zhang, Y., Baig, E. & Williams, D. B. Functions of ERp57 in the folding and assembly of major histocompatibility complex class I molecules. J Biol Chem 281:14622–14631 (2006).

    Article  CAS  PubMed  Google Scholar 

  28. Soldà, T., Garbi, N., Hämmerling, G. J. & Molinari, M. Consequences of ERp57 deletion on oxidative folding of obligate and facultative clients of the calnexin cycle. J Biol Chem 281:6219–6226 (2006).

    Article  PubMed  Google Scholar 

  29. Cox, J. L. et al. Banf1 is required to maintain the self-renewal of both mouse and human embryonic stem cells. J Cell Sci 124:2654–2665 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Trachootham, D., Alexandre, J. & Huang, P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8:579–591 (2009).

    Article  CAS  PubMed  Google Scholar 

  31. Vitória, A. P., Lea, P. J. & Azevedo, R. A. Antioxidant enzymes responses to cadmium in radish tissues. Phytochemistry 57:701–710 (2001).

    Article  PubMed  Google Scholar 

  32. Ryu, A. R., Wang, W. Y. & Lee, M. Y. Differential protein expression associated with photodynamic therapy using chlorin e6. Mol Cell Toxicol 10:423–431 (2014).

    Article  CAS  Google Scholar 

  33. Lee, M. Y. & Shin, H. W. Cadmium-induced changes in antioxidant enzymes from the marine alg Nannochloropsis oculata. J Appl Phycol 15:13–19 (2003).

    Article  CAS  Google Scholar 

  34. Rao, M. V., Paliyath, G. & Ormrod, D. P. Ultraviolet-B and ozone-induced biochemical changes in antioxidant enzymes o Arabidopsis thaliana. Plant Physiol 110:125–136 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Asada, K., Takahashi, M. & Nagate, M. Assay and inhibitors of spinach superoxide dismutase. Agric Biol Chem 38:471–473 (1974).

    Article  CAS  Google Scholar 

  36. Cejková, J., Stípek, S., Crkovská, J. & Ardan, T. Changes of superoxide dismutase, catalase and glutathione peroxidase in the corneal epithelium after UVB rays. Histochemical and biochemical study. Histol Histopathol 15:1043–1050 (2000).

    PubMed  Google Scholar 

  37. Kang, K. S., Lim, C. J., Han, T. J., Kim, J. C. & Jin, C. D. Changes in the isozyme composition of antioxidant enzymes in response to aminotriazole in leaves o Arabidopsis thaliana. J Plant Biology 42:187–193 (1999).

    Article  CAS  Google Scholar 

  38. Laemmli, U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685 (1970).

    Article  CAS  PubMed  Google Scholar 

  39. Woodbury, W., Spencer, A. K. & Stahmann, M. A. An improved procedure using ferricyanide for detecting catalase isozymes. Anal Biochem 44:301–305 (1971).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Science, SoonChunHyang University, Asan, Chungnam, 31538, Korea

    Ji-Hae Kim, A.-Reum Ryu, Min-Joo Kang & Mi-Young Lee

  2. Departments of Medical Biotechnology, SoonChunHyang University, Asan, Chungnam, 31538, Korea

    Mi-Young Lee

Authors
  1. Ji-Hae Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A.-Reum Ryu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Min-Joo Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mi-Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mi-Young Lee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, JH., Ryu, AR., Kang, MJ. et al. Berberine-induced changes in protein expression and antioxidant enzymes in melanoma cells. Mol. Cell. Toxicol. 12, 53–61 (2016). https://doi.org/10.1007/s13273-016-0008-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-016-0008-z

Keywords

Search

Navigation