Isolation of Potential Compound from the Leaves of Elytraria acaulis and Evaluating Its Therapeutic Properties Using In Vitro Studies Against Ovarian Cancer.

The present study was designed to isolate a potential compound from the extracts of Elytraria acaulis (E. acaulis) for ovarian cancer. n-Hexane, ethyl acetate, chloroform, acetone and methanol extract were taken using the Soxhlet method. Thin layer, column chromatography, NMR and MASS studies were done for the isolation and structural characterization of the compound. Finally, the novel compound (Z)-3-(2-methyl-3-oxoprop-1-en-1-yl) phenyl heptanoate was identified. MTT assay, cell morphology and cell cycle analysis were done to evaluate the anticancer property of the compound. In the MTT assay, the percentage of the cell viability treated with the isolated compound was decreased while increasing the concentration of the compound. Cancer cells treated with the isolated compound showed distinct morphological changes when compared to the control untreated cells. In the cell cycle analysis, the isolated compound induced a significant increase in the percentage of cells in G0/G1 phase and a decrease in the percentage of cells in the S phase and G2-M phase of the PA 1 cell lines. The cell cycle arrest induced by the isolated compound may account for its antiproliferative capacity. Hence, the novel compound isolated from E. acaulis can be a potent candidate in the designing of anticancer drugs.

Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata.

Matrix metalloproteinases (MMPs) are pivotal for cancer cell migration and metastasis which are generally over-expressed in such cell types. Many drugs targeting MMPs do so by binding to the conserved catalytic domains and thus exhibit poor selectivity due to domain-similarities with other proteases. We report herein the binding of a novel compound [3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl 9Z, 12Z-octadeca-9, 12-dienoate; Mol. wt: 516.67 Da], (C1), isolated from a seagrass, Cymodocea serrulata to the unconserved hemopexin-like (PEX) domain of MMP2 (- 9.258 kcal/mol). MD simulations for 25 ns, suggest stable ligand-target binding. In addition, C1 killed an ovarian cancer cell line, PA1 at IC50: 5.8 µM (lesser than Doxorubicin: 8.6 µM) and formed micronuclei, apoptotic bodies and nucleoplasmic bridges whilst causing DNA laddering, S and G2/M phase dual arrests and MMP disturbance, suggesting intrinsic apoptosis. The molecule increased mRNA transcripts of BAX and BAD and down-regulated cell survival genes, Bcl-xL, Bcl-2, MMP2 and MMP9. The chemical and structural details of C1 were deduced through FT-IR, GC-MS, ESI-MS, 1H and 13C NMR [both 1D and 2D] spectra.

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.

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 ±â€¯5.8 µM for cancerous A549 cell lines, whilst not targeting non-cancerous vero cells [IC50: 183.6 ±â€¯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.