Dataset Information

Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study.

ABSTRACT: Matrix metalloproteinase9 (MMP9) is known to be highly expressed during metastatic cancer where most known potential inhibitors failed in the clinical trials. This study aims to select local plants in our state, as anti-breast cancer agent with hemopexin-like domain of MMP9 (PEX9) as the selective protein target. In silico screening for PEX9 inhibitors was performed from our in house-natural compound database to identify the plants. The selected plants were extracted using methanol and then a step-by-step in vitro screening against MMP9 was performed from its crude extract, partitions until fractions using FRET-based assay. The partitions were obtained by performing liquid-liquid extraction on the methanol extract using n-hexane, ethylacetate, n-butanol, and water representing nonpolar to polar solvents. The fractions were made from the selected partition, which demonstrated the best inhibition percentage toward MMP9, using column chromatography. Of the 200 compounds screened, 20 compounds that scored the binding affinity -11.2 to -8.1 kcal/mol toward PEX9 were selected as top hits. The binding of these hits were thoroughly investigated and linked to the plants which they were reported to be isolated from. Six of the eight crude extracts demonstrated inhibition toward MMP9 with the IC50 24 to 823 µg/mL. The partitions (1 mg/mL) of Ageratum conyzoides aerial parts and Ixora coccinea leaves showed inhibition 94% and 96%, whereas their fractions showed IC50 43 and 116 µg/mL, respectively toward MMP9. Using MTT assay, the crude extract of Ageratum exhibited IC50 22 and 229 µg/mL against 4T1 and T47D cell proliferations, respectively with a high safety index concluding its potential anti-breast cancer from herbal.

SUBMITTER: Hariono M

PROVIDER: S-EPMC7587335 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study.

Hariono Maywan M Rollando Rollando R Karamoy Jasson J Hariyono Pandu P Atmono M M Djohan Maria M Wiwy Wiwy W Nuwarda Rina R Kurniawan Christopher C Salin Nurul N Wahab Habibah H

Molecules (Basel, Switzerland) 20201014 20

Matrix metalloproteinase9 (MMP9) is known to be highly expressed during metastatic cancer where most known potential inhibitors failed in the clinical trials. This study aims to select local plants in our state, as anti-breast cancer agent with hemopexin-like domain of MMP9 (PEX9) as the selective protein target. In silico screening for PEX9 inhibitors was performed from our in house-natural compound database to identify the plants. The selected plants were extracted using methanol and then a st ...[more]

PMID: 33066411

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Project description:Mechanical interactions during angiogenesis, i.e., traction applied by neovessels to the extracellular matrix and the corresponding deformation, are important regulators of growth and neovascularization. We have previously designed, implemented, and validated a coupled model of angiogenesis in which a discrete microvessel growth model interacts with a continuous finite element mesh through the application of local remodeling sprout stresses (Edgar et al. in Biomech Model Mechanobiol, 2014). However, the initial implementation of this framework does not take matrix density into account when determined these remodeling stresses and is therefore insufficient for the study of angiogenesis within heterogeneous matrix environments such as those found in vivo. The objective of this study was to implement sensitivity to matrix density in the active stress generation within AngioFE in order to allow the study of angiogenic growth within a heterogeneous density environment. We accomplished this by scaling active sprout stresses relative to local matrix density using a scaling factor previously determined from experimental data. We then exercised the new functionality of the model by simulating angiogenesis within four different scenarios: homogeneous density, a narrow gap model, and matrix density gradient, and a construct subjected to repeated loading/unloading and preconditioning. These numerical experiments predicted heterogeneous matrix density in the initially homogeneous case, the closure and alignment of microvessels along a low-density gap, the formation of a unique cap-like structure during angiogenesis within a density gradient, and the alignment of microvessels in the absence of applied load due to preconditioning. The result of these in silico investigations demonstrate how matrix heterogeneity affects neovascularization and matrix deformation and provides a platform for studying angiogenesis in complicated and multi-faceted mechanical environments that microvessels experience in vivo.

Dataset Information

Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study.

Publications

Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: In Silico and In Vitro Study.

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