Palma Taís Vidal, Bianchin Nathiele Botari, de Oliveira Juliana Sorraila, Assmann Charles Elias, das Neves Oliveira Mona, Schetinger Maria Rosa Chitolina, Morsch Vera Maria, Ulrich Henning, Pillat Micheli Mainardi, de Andrade Cinthia Melazzo
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.
Biolinker Synthetic Biology IERLI, São Paulo, Brazil.
Mol Biol Rep. 2022 Mar;49(3):2037-2046. doi: 10.1007/s11033-021-07022-4. Epub 2021 Dec 3.
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.
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.
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.
黑色素瘤是皮肤癌中最致命的形式，在过去几十年中其发病率显著增加。由于黑色素瘤具有极强的侵袭性和高转移能力，肿瘤细胞具有很强的耐药性，导致其治疗困难。黄连素（BBR）是一种异喹啉生物碱，存在于多种药用植物中，已在多种疾病中进行了研究，具有抗菌、抗糖尿病、抗炎特性和抗肿瘤作用。
在SK-MEL-28细胞中，50μM BBR处理24小时可使细胞活力降低50%。该浓度通过早期凋亡和坏死导致细胞死亡，同时DNA损伤指数增加。BBR使G1/G0期细胞比例增加（*p＜0.05），S期细胞百分比降低（p＜0.005）。与未处理的对照组相比，该生物碱使活性氧（ROS）生成增加（****p＜0.001），同时活化的半胱天冬酶3和磷酸化p53蛋白水平升高。此外，与未处理的对照组相比，BBR显著增强了细胞外调节蛋白激酶（ERK）以及促炎和抗炎细胞因子的表达。
BBR具有重要的抗增殖作用，可能单独或作为辅助治疗成为黑色素瘤治疗的有希望的候选药物，黑色素瘤是一种发病率高且致死率高的癌症。
