Technological Development Center (Centro de Desenvolvimento Tecnológico - ®CDTec), Federal University of Pelotas (Universidade Federal de Pelotas-UFPel), Pelotas, Brazil.
Institute of Biosciences, Humanities and Exact Sciences (IBILCE), Department of Biology, São Paulo State University (UNESP), São José do Rio Preto, Brazil.
Photodiagnosis Photodyn Ther. 2020 Dec;32:102045. doi: 10.1016/j.pdpdt.2020.102045. Epub 2020 Oct 1.
Cervical cancer is a serious worldwide health problem. In view of the potentially harmful effects of current conventional therapies, photodynamic therapy may be an option as it is a minimally invasive therapy and can promote selective cytotoxic activity for neoplastic cells in the target tissue., Berberine (BBR) as an isolated molecule is a natural compound that has antineoplastic properties and potential action as a photosensitizer agent. The purpose of this study was to evaluate the use of berberine as a photosensitizer in photodynamic therapy (PDT) protocols and observe the effects produced by this association in cervical carcinoma cells and in immortalized keratinocytes. Incubation with 2.5 μM berberine promoted less than 10 % of cellular death in both cell lines studied. In addition, by fluorescence microscopy, we demonstrated that berberine was internalized by the cells, and after a period of 48 h, it was still present in the intracellular environment preferentially localized in the cytoplasm. After photodynamic therapy using berberine as a photosensitizer and visible light activation at 447 (±10) nm, we observed a phototoxic effect, which resulted in 19.84 % cell viability for Caski cells and 47.22 % cell viability for HaCaT. Treatment with berberine associated with photodynamic therapy promoted an increase in the production of reactive species of oxygen (ROS) and caspase-3 activity, indicating a preferential cell death mechanism by caspase-dependent apoptosis. Therefore, we demonstrated that berberine is an efficient photosensitizer and that its association with photodynamic therapy may be a potential anticancer treatment strategy for cervical cancer.
宫颈癌是一个严重的全球健康问题。鉴于目前常规疗法可能产生的有害影响,光动力疗法可能是一种选择,因为它是一种微创疗法,可以促进靶组织中肿瘤细胞的选择性细胞毒性活性。小檗碱 (BBR) 作为一种分离的分子是一种具有抗肿瘤特性的天然化合物,具有作为光敏剂的潜在作用。本研究旨在评估小檗碱作为光动力疗法 (PDT) 方案中的光敏剂的用途,并观察这种联合在宫颈癌和永生化角质形成细胞中产生的作用。在两种研究的细胞系中,孵育 2.5 μM 小檗碱仅导致小于 10%的细胞死亡。此外,通过荧光显微镜,我们证明小檗碱被细胞内化,并且在 48 小时后,它仍存在于细胞内环境中,优先定位于细胞质中。在用小檗碱作为光敏剂并用 447(±10)nm 可见光激活进行光动力疗法后,我们观察到光毒性作用,导致 Caski 细胞的细胞活力为 19.84%,HaCaT 细胞的细胞活力为 47.22%。小檗碱联合光动力疗法治疗可促进活性氧 (ROS) 的产生和 caspase-3 活性增加,表明 caspase 依赖性细胞凋亡是一种优先的细胞死亡机制。因此,我们证明小檗碱是一种有效的光敏剂,其与光动力疗法的联合可能是宫颈癌的一种潜在的抗癌治疗策略。