Department of Biotechnology, Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600 116, India.
Central Research Facility (CRF), Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600 116, India.
Phytomedicine. 2019 Aug;61:152858. doi: 10.1016/j.phymed.2019.152858. Epub 2019 Feb 5.
The present investigation looks at the most likely possibilities of usage of a naturally occurring photosynthetic pigment, Pheophytin a, from the seagrass, Syringodium isoetifolium, for plausible use as human TSPO ligand.
Pheophytin a isolated in our laboratory previously was administered to A549 cell lines in vitro to examine its effects on cell migrations, DNA, cell cycle, Mitochondrial Membrane Potential and gene expressions. In silico tools were used to predict the nature of the compound and target binding.
Pheophytin a hadIC values of 22.9 ± 5.8 µM for cancerous A549 cell lines, whilst not targeting non-cancerous vero cells [IC: 183.6 ± 1.92 µM]. Pheophytin a hindered cellular migration, fragmented DNA, arrested cell cycle precisely at S phase, reduced ∆ψ and directed mRNA expressions toward apoptosis. In silico tools indicate that the compound binds to TSPO with high effectiveness to collapse ∆ψ(which is proved using wet lab experiments) to promote mitophagy.
Hence Pheophytin a could be seen as a possible TSPO ligand for targeting metastatic alveolar cancers like A549 via intrinsic apoptotic pathway.
Given the inherent non-toxic nature of the compound and easy extractability from almost all autotrophic eukaryotes, one could be confident to testing in animal models.
本研究探讨了一种天然光合色素脱镁叶绿素 a 最有可能的用途,即从海草 Syringodium isoetifolium 中提取,作为人类 TSPO 配体的合理应用。
我们实验室之前分离出的脱镁叶绿素 a 被用于体外 A549 细胞系,以研究其对细胞迁移、DNA、细胞周期、线粒体膜电位和基因表达的影响。使用计算工具预测化合物的性质和靶标结合。
脱镁叶绿素 a 对癌细胞 A549 细胞系的 IC 值为 22.9±5.8µM,而对非癌细胞 vero 细胞无靶向作用[IC:183.6±1.92µM]。脱镁叶绿素 a 抑制细胞迁移,使 DNA 碎片化,将细胞周期精确阻滞在 S 期,降低∆ψ,并促使 mRNA 表达向细胞凋亡方向发展。计算工具表明,该化合物与 TSPO 结合具有高有效性,可使∆ψ崩溃(这通过湿实验室实验证明),从而促进线粒体自噬。
因此,脱镁叶绿素 a 可以被视为一种潜在的 TSPO 配体,通过内在凋亡途径靶向转移性肺泡癌,如 A549。
鉴于该化合物固有的非毒性性质和几乎从所有自养真核生物中都可轻易提取的特点,人们有信心在动物模型中进行测试。