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核黄素单核苷酸和黄素腺嘌呤二核苷酸的蓝光诱导活性氧对 HeLa 细胞致死性的影响。

Blue light induced reactive oxygen species from flavin mononucleotide and flavin adenine dinucleotide on lethality of HeLa cells.

机构信息

Institute of Medical Sciences, Tzu-Chi University, Hualien 970, Taiwan; Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 970, Taiwan.

Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 970, Taiwan.

出版信息

J Photochem Photobiol B. 2017 Aug;173:325-332. doi: 10.1016/j.jphotobiol.2017.06.014. Epub 2017 Jun 13.

Abstract

Photodynamic therapy (PDT) is a safe and non-invasive treatment for cancers and microbial infections. Various photosensitizers and light sources have been developed for clinical cancer therapies. Flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are the cofactor of enzymes and are used as photosensitizers in this study. Targeting hypoxia and light-triggering reactive oxygen species (ROS) are experimental strategies for poisoning tumor cells in vitro. HeLa cells are committed to apoptosis when treated with FMN or FAD and exposed to visible blue light (the maximum emitted wavelength of blue light is 462nm). Under blue light irradiation at 3.744J/cm (=0.52mW/cm irradiated for 2h), the minimal lethal dose is 3.125μM and the median lethal doses (LD) for FMN and FAD are 6.5μM and 7.2μM, respectively. Individual exposure to visible blue light irradiation or riboflavin photosensitizers does not produce cytotoxicity and no side effects are observed in this study. The western blotting results also show that an intrinsic apoptosis pathway is activated by the ROS during photolysis of riboflavin analogues. Blue light triggers the cytotoxicity of riboflavins on HeLa cells in vitro. Based on these results, this is a feasible and efficient of PDT with an intrinsic photosensitizer for cancer research.

摘要

光动力疗法(PDT)是一种安全、非侵入性的癌症和微生物感染治疗方法。已经开发出各种光敏剂和光源用于临床癌症治疗。黄素单核苷酸(FMN)和黄素腺嘌呤二核苷酸(FAD)是酶的辅因子,在本研究中用作光敏剂。针对缺氧和光触发的活性氧(ROS)是体外毒害肿瘤细胞的实验策略。当用 FMN 或 FAD 处理并暴露于可见光蓝光(蓝光最大发射波长为 462nm)时,HeLa 细胞会被诱导凋亡。在 3.744J/cm(=0.52mW/cm 照射 2 小时)的蓝光照射下,最小致死剂量为 3.125μM,FMN 和 FAD 的半数致死剂量(LD)分别为 6.5μM 和 7.2μM。单独暴露于可见光蓝光照射或核黄素光敏剂不会产生细胞毒性,在本研究中也没有观察到任何副作用。Western blot 结果还表明,ROS 在光解核黄素类似物时激活了内在凋亡途径。蓝光在体外触发 HeLa 细胞中核黄素的细胞毒性。基于这些结果,这是一种可行且有效的 PDT 方法,使用内在光敏剂进行癌症研究。

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