Yantai Key Laboratory of Pharmacology of Traditional Chinese Medicine in Tumor Metabolism, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, 264003, Yantai, China.
Jiangsu College of Nursing, 9 Science and Technology Avenue, Huaian, 223005, Jiangsu, China.
Biomed Pharmacother. 2021 Jan;133:111042. doi: 10.1016/j.biopha.2020.111042. Epub 2020 Dec 8.
The application of photodynamic therapy (PDT) for the treatment of skin diseases has been receiving much attention. Here, we examined the anti-tumor effect of a novel porphyrin-based photosensitizer TBPoS-2OH in the malignant melanoma A375 and B16 cells. TBPoS-2OH has obvious cell photo-cytotoxicity, but it has low cell dark-cytotoxicity. Further research showed that TBPoS-2OH is enriched in lysosomes after being taken up by cells. Subsequently, the apoptotic rates were significantly increased in TBPoS-2OH-treated A375 and B16 cells. The specific mechanism may be that after receiving light stimulation, TBPoS-2OH could effectively increase the level of intracellular reactive oxygen species (ROS), thereby activating mitochondrial apoptosis pathway-related proteins in A375 and B16 cells. We found an increase in the content of cytochrome C in the cytoplasm, and the levels of related proteins, such as cleaved caspase-3, cleaved caspase-9, and cleaved PARP1, were significantly increased in TBPoS-2OH-treated cells. These results indicated that the new compound TBPoS-2OH could be developed and become an alternative drug for the treatment of melanoma. Some reference ideas for the development of new photosensitizers are also provided.
光动力疗法(PDT)在皮肤病治疗中的应用受到了广泛关注。在这里,我们研究了新型卟啉类光敏剂 TBPoS-2OH 在恶性黑色素瘤 A375 和 B16 细胞中的抗肿瘤作用。TBPoS-2OH 对细胞具有明显的光细胞毒性,但暗细胞毒性较低。进一步的研究表明,TBPoS-2OH 被细胞摄取后在溶酶体中富集。随后,TBPoS-2OH 处理的 A375 和 B16 细胞的凋亡率显著增加。其特定机制可能是,TBPoS-2OH 在接收到光刺激后能够有效增加细胞内活性氧(ROS)的水平,从而激活 A375 和 B16 细胞中线粒体凋亡途径相关蛋白。我们发现细胞质中细胞色素 C 的含量增加,并且 TBPoS-2OH 处理的细胞中相关蛋白(如裂解的 caspase-3、裂解的 caspase-9 和裂解的 PARP1)的水平显著增加。这些结果表明,新型化合物 TBPoS-2OH 可被开发成为治疗黑色素瘤的替代药物。本研究还为新型光敏剂的开发提供了一些参考思路。