Taís Vidal Palma1, Nathiele Botari Bianchin2, Juliana Sorraila de Oliveira2, Charles Elias Assmann2, Mona das Neves Oliveira3, Maria Rosa Chitolina Schetinger2, Vera Maria Morsch2, Henning Ulrich4, Micheli Mainardi Pillat5, Cinthia Melazzo de Andrade6,7. 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. taisvid@hotmail.com. 2. 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. 3. Biolinker Synthetic Biology IERLI, São Paulo, Brazil. 4. Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil. 5. 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.pillat@ufsm.br. 6. 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. cmelazzoandrade1@gmail.com. 7. 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. cmelazzoandrade1@gmail.com.
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.
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.
Authors: Dirk Schadendorf; David E Fisher; Claus Garbe; Jeffrey E Gershenwald; Jean-Jacques Grob; Allan Halpern; Meenhard Herlyn; Michael A Marchetti; Grant McArthur; Antoni Ribas; Alexander Roesch; Axel Hauschild Journal: Nat Rev Dis Primers Date: 2015-04-23 Impact factor: 52.329