A natural anticancer pigment,Pheophytin a,from a seagrass acts as a high affinity human mitochondrial translocator protein (TSPO) ligand, in silico, to reduce mitochondrial membrane Potential (∆ψmit) in adenocarcinomic A549 cells

•We prove that the accessory photosynthetic pigment, Pheophytin a made lung cancer cell lines, A549 to undergo apoptotic mode of death.•The compound initiated the formation of apoptotic bodies, fragmented DNA, inhibited cellular migration and bulked the cells at S phase and the cell cycle did not fu...

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Published in:	Phytomedicine (Stuttgart) Vol. 61; p. 152858
Main Authors:	Shailaja, V.L., Christina, V.S., Mohanapriya, C.D., Sneha, P., Lakshmi Sundaram, R., Magesh, R., George Priya Doss, C., Gnanambal, K. Mary Elizabeth
Format:	Journal Article
Language:	English
Published:	Germany Elsevier GmbH 01-08-2019
Subjects:	A549 Cells ADMET Alismatales - chemistry Animals Antineoplastic Agents, Phytogenic - chemistry Antineoplastic Agents, Phytogenic - pharmacokinetics Antineoplastic Agents, Phytogenic - pharmacology Apoptosis - drug effects Cell Cycle - drug effects Cell cycle arrest Cell Movement - drug effects Cell Movement - genetics Chlorocebus aethiops Computer Simulation Drug Screening Assays, Antitumor Gene Expression Regulation, Neoplastic - drug effects Humans Ligands Membrane Potential, Mitochondrial - drug effects Molecular docking Molecular Docking Simulation Molecular dynamics simulation Pheophytin a Pheophytins - chemistry Pheophytins - pharmacokinetics Pheophytins - pharmacology Receptors, GABA - metabolism TSPO Vero Cells MMP Pheophytin a Cell cycle arrest TSPO Molecular dynamics simulation ADMET Molecular docking
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Summary:	•We prove that the accessory photosynthetic pigment, Pheophytin a made lung cancer cell lines, A549 to undergo apoptotic mode of death.•The compound initiated the formation of apoptotic bodies, fragmented DNA, inhibited cellular migration and bulked the cells at S phase and the cell cycle did not further thereafter.•Using in silico tools, we prove that Pheoptyin a binds with high affinity to TSPO protein and in vitro assays inidcated reduction of ∆ψmit to disrupt mitochondrial membrane.•Hence this easily extractable, non-toxic (proved using ADMET) pigment could be suggested as a plausible TSPO ligand. 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 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. 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. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0944-7113 1618-095X
DOI:	10.1016/j.phymed.2019.152858