Suprihadi Arif, Pustimbara Anantya, Ogura Shun-Ichiro
Tokyo Institute of Technology, School of Life Science and Technology, 4259 Midori-ku, Yokohama, Kanagawa 226-8501, Japan.
Photodiagnosis Photodyn Ther. 2022 Dec;40:103055. doi: 10.1016/j.pdpdt.2022.103055. Epub 2022 Aug 4.
Mitochondrial dysfunctions are related to cancer development.. 5-aminolevulinic acid (ALA) is used for photodynamic therapy (PDT). In this PDT, protoporphyrin IX (PpIX), which is converted from ALA, can generate reactive oxygen species (ROS) that kill the cancer cell. ALA is also reported to promote cytochrome c oxidase (COX) activity, which can generate ROS itself. Therefore, this study focused on the effect of ALA during PDT. In addition, in the previous study, sodium ferrous citrate (SFC) is reported to increase COX activity. So, this study also aims to improve the COX activity by the addition of SFC that can promote ROS generation, which has a cytotoxic effect.
In this study, we used ALA and SFC, then evaluated the effects of the treatment on the human gastric cancer cell line MKN45, including the induction of cell death.
This study showed that treatment with ALA and SFC increases intracellular heme and heme proteins. Moreover, COX activity was promoted, resulting in the production of intracellular reactive oxygen species (ROS), which eventually reduced the cell viability in human gastric cancer cell line MKN45.
Our study can detect ROS generation with ALA and SFC. Furthermore, we found this generation of ROS has a cytotoxic effect. Therefore, this phenomenon contributes to the effect of PDT.
线粒体功能障碍与癌症发展有关。5-氨基酮戊酸(ALA)用于光动力疗法(PDT)。在这种光动力疗法中,由ALA转化而来的原卟啉IX(PpIX)可产生活性氧(ROS),从而杀死癌细胞。据报道,ALA还可促进细胞色素c氧化酶(COX)的活性,而该酶本身也能产生活性氧。因此,本研究聚焦于ALA在光动力疗法中的作用。此外,在之前的研究中,据报道柠檬酸亚铁钠(SFC)可提高COX活性。所以,本研究还旨在通过添加可促进ROS生成且具有细胞毒性作用的SFC来提高COX活性。
在本研究中,我们使用了ALA和SFC,然后评估了该处理对人胃癌细胞系MKN45的影响,包括细胞死亡的诱导情况。
本研究表明,用ALA和SFC处理可增加细胞内血红素和血红素蛋白。此外,COX活性得到促进,导致细胞内活性氧(ROS)的产生,最终降低了人胃癌细胞系MKN45的细胞活力。
我们的研究能够检测到ALA和SFC产生活性氧的情况。此外,我们发现这种活性氧的产生具有细胞毒性作用。因此,这一现象有助于光动力疗法的效果。