V L Shailaja1, V S Christina1, C D Mohanapriya2, P Sneha3, R Lakshmi Sundaram2, R Magesh1, C George Priya Doss4, K Mary Elizabeth Gnanambal5. 1. Department of Biotechnology, Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600 116, India. 2. Central Research Facility (CRF), Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600 116, India. 3. Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore 632014, India. 4. Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore 632014, India. Electronic address: georgepriyadoss@vit.ac.in. 5. Department of Biotechnology, Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai 600 116, India. Electronic address: drelizabethrajesh@sriramachandra.edu.in.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: Pheophytin a hadIC50 values of 22.9 ± 5.8 µM for cancerous A549 cell lines, whilst not targeting non-cancerous vero cells [IC50: 183.6 ± 1.92 µM]. Pheophytin a hindered cellular migration, fragmented DNA, arrested cell cycle precisely at S phase, reduced ∆ψmit and directed mRNA expressions toward apoptosis. In silico tools indicate that the compound binds to TSPO with high effectiveness to collapse ∆ψmit(which is proved using wet lab experiments) to promote mitophagy. CONCLUSION: Hence Pheophytin a could be seen as a possible TSPO ligand for targeting metastatic alveolar cancers like A549 via intrinsic apoptotic pathway. GENERAL SIGNIFICANCE: 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.
BACKGROUND: 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 humanTSPO ligand. METHODS: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. RESULTS:Pheophytin a hadIC50 values of 22.9 ± 5.8 µM for cancerous A549 cell lines, whilst not targeting non-cancerous vero cells [IC50: 183.6 ± 1.92 µM]. Pheophytin a hindered cellular migration, fragmented DNA, arrested cell cycle precisely at S phase, reduced ∆ψmit and directed mRNA expressions toward apoptosis. In silico tools indicate that the compound binds to TSPO with high effectiveness to collapse ∆ψmit(which is proved using wet lab experiments) to promote mitophagy. CONCLUSION: Hence Pheophytin a could be seen as a possible TSPO ligand for targeting metastatic alveolar cancers like A549 via intrinsic apoptotic pathway. GENERAL SIGNIFICANCE: 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.
Authors: V S Christina; R Lakshmi Sundaram; V Sivamurugan; D Thirumal Kumar; C D Mohanapriya; V L Shailaja; S P Thyagarajan; C George Priya Doss; K Mary Elizabeth Gnanambal Journal: Sci Rep Date: 2021-06-01 Impact factor: 4.379