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Berberine increases the expression of cytokines and proteins linked to apoptosis in human melanoma cells

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Abstract

Background

Melanoma is the most lethal form of skin cancer, and its incidence has increased considerably in the last decades. Melanoma presents difficult treatment with strong resistance of tumor cells, due to its extremely invasive nature with high capacity to metastases. Berberine (BBR), an isoquinoline alkaloid, is a molecule found in several medicinal plants, and has been studied in several diseases, demonstrating antimicrobial, antidiabetic and anti-inflammatory properties and anti-tumorigenic effects.

Methods and results

In SK-MEL-28 cells, 50 μM BBR treatment for 24 h decreased cell viability by 50 percent. This concentration generated cell death both by early apoptosis and necrosis, with an increase in the DNA damage index. BBR increased (*p < 0.05) the proportion of cells in G1/G0 phase and decreased (###p < 0.005) the percentage of cells in S phase. The alcaloid increased (****p < 0.001) ROS production compared to untreated controls with an increase in activated caspase 3 and phosphorylated p53 protein levels. In addition, BBR significantly enhanced ERK as well as both pro- and anti-inflammatory cytokine expression compared to untreated controls.

Conclusions

BBR has important antiproliferative effects and may be alone or in adjunct therapy a promising candidate for melanoma treatment, a cancer with great incidence and high lethality.

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Acknowledgements

TVP is grateful for doctoral fellowships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Programa de Excelência Acadêmica (CAPES/PROEX-N°: 88882.182140/2018-01). MMP acknowledges grant support by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS Proj. No. 20255100002535). HU acknowledges grant support by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP Proj. No. 2018/07366-4).

Funding

This study was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Programa de Excelência Acadêmica (CAPES/PROEX-N°: 88882.182140/2018-01), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS Proj. No. 20255100002535) and by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP Proj. No. 2018/07366-4).

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Authors and Affiliations

  1. Department of Chemistry, Center for Natural and Exact Sciences, Postgraduate Program in Biological Sciences: Biochemistry Toxicological, Federal University of Santa Maria, Santa Maria, RS, Brazil

    Taís Vidal Palma, Nathiele Botari Bianchin, Juliana Sorraila de Oliveira, Charles Elias Assmann, Maria Rosa Chitolina Schetinger, Vera Maria Morsch & Cinthia Melazzo de Andrade

  2. Biolinker Synthetic Biology IERLI, São Paulo, Brazil

    Mona das Neves Oliveira

  3. Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil

    Henning Ulrich

  4. Department of Microbiology and Parasitology, Postgraduate Program in Pharmacology and Postgraduate Program in Pharmaceutical Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil

    Micheli Mainardi Pillat

  5. Department of Small Animal Clinic, Center of Rural Sciences, Federal University of Santa Maria-RS, Room 121, Veterinary Hospital Building, Avenue Roraima n° 1000, Santa Maria, RS, 97105900, Brazil

    Cinthia Melazzo de Andrade

Authors
  1. Taís Vidal Palma
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  2. Nathiele Botari Bianchin
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Contributions

Conceptualization: TVP; methodology: TVP, NBB, JSO, CEA, MO, MCS, VMM, HU, MMP, CMA; investigation: TVP, NBB, JSO, CEA, MO, MCS, VMM, HU, MMP, CMA; funding acquisition: TVP, MMP, HU; Supervision: TVP, MMP, CMA; writing—original draft: TVP, HU, MMP, CMA; Writing—review and editing: TVP, HU, MMP, CMA.

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Correspondence to Taís Vidal Palma, Micheli Mainardi Pillat or Cinthia Melazzo de Andrade.

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Palma, T.V., Bianchin, N.B., de Oliveira, J.S. et al. Berberine increases the expression of cytokines and proteins linked to apoptosis in human melanoma cells. Mol Biol Rep 49, 2037–2046 (2022). https://doi.org/10.1007/s11033-021-07022-4

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