Dataset Information

Alpinumisoflavone against cancer pro-angiogenic targets: In silico, In vitro, and In ovo evaluation.

ABSTRACT:

Background

Breast cancer is currently the world's most predominant malignancy. In cancer progression, angiogenesis is a requirement for tumor growth and metastasis.Alpinumisoflavone (AIF), a bioactive isoflavonoid, exhibited good binding affinity with the angiogenesis pathway's druggable target through molecular docking.

Objectives

To confirm AIF's angiogenesis inhibitory activity, cytotoxic potential toward breast cancer cells, and druggability.

Methods

Antiangiogenic activity was evaluated in six pro-angiogenic proteins in vitro, duck chorioallantoic membrane (CAM) in ovo, molecular docking and druggability in silico.

Results

Findings showed that AIF significantly inhibited (p = < 0.001) the HER2(IC₅₀ = 2.96 µM), VEGFR-2(IC₅₀ = 4.80 µM), MMP-9(IC₅₀ = 23.00 µM), FGFR4(IC₅₀ = 57.65 µM), EGFR(IC₅₀ = 92.06 µM) and RET(IC₅₀ = > 200 µM) activity in vitro.AIF at 25 µM-200 µM significantly inhibited (p = < 0.001) the total number of branch points (IC₅₀ = 14.25 μM) and mean length of tubule complexes (IC₅₀ = 3.52 μM) of duck CAM comparable (p = > 0.001) with the positive control 200 µM celecoxib on both parameters.AIF inhibited the growth of the estrogen-receptor-positive (ER +) human breast cancer cells (MCF-7) by 44.92 ± 1.79% at 100 µM while presenting less toxicity to human dermal fibroblast neonatal (HDFn) normal cells.The positive control 100 µM doxorubicin showed 86.66 ± 0.93% and 92.97 ± 1.27% inhibition with MCF-7 (IC₅₀ = 3.62 μM) and HDFn, (IC₅₀ = 27.16 μM) respectively.In docking, AIF has the greatest in silico binding affinity on HER2 (-10.9 kcal/mol) among the key angiogenic molecules tested. In silico rat oral LD₅₀ calculation indicates that AIF is moderate to slightly toxic at 146.4 mg/kg with 1.1 g/kg and 20.1 mg/kg upper and lower 95% confidence limits. Lastly, it sufficiently complies with Lipinski's, Veber's, Egan's, Ghose's, and Muegge's Rule, supporting its oral drug-like property.

Conclusion

This study revealed that AIF possesses characteristics of a phytoestrogen compound with significant binding affinity, inhibitory activity against pro-angiogenic proteins, and cytotoxic potential against ER + breast cancer cells.The acceptable and considerable safety and drug-likeness profiles of AIF are worthy of further confirmation in vivo and advanced pre-clinical studies so that AIF can be elevated as a promising molecule for breast cancer therapy.

SUBMITTER: Alos HC

PROVIDER: S-EPMC9715906 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Alpinumisoflavone against cancer pro-angiogenic targets: In silico, In vitro, and In ovo evaluation.

Alos Honeymae C HC Billones Junie B JB Castillo Agnes L AL Vasquez Ross D RD

Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 20220804 2

<h4>Background</h4>Breast cancer is currently the world's most predominant malignancy. In cancer progression, angiogenesis is a requirement for tumor growth and metastasis.Alpinumisoflavone (AIF), a bioactive isoflavonoid, exhibited good binding affinity with the angiogenesis pathway's druggable target through molecular docking.<h4>Objectives</h4>To confirm AIF's angiogenesis inhibitory activity, cytotoxic potential toward breast cancer cells, and druggability.<h4>Methods</h4>Antiangiogenic acti ...[more]

PMID: 35925539

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Project description:Liver cancer is the second most common cause of cancer-induced deaths worldwide. Liver cirrhosis and cancer are a consequence of the abnormal angio-architecture formation of liver and formation of new blood vessels. This angiogenesis is driven by overexpression of hypoxia-inducible factor 1-alpha (Hif1-α) and vascular endothelial growth factor (VEGF). Apart from this, protein kinase B (Akt) is also impaired in liver cancer. Despite the advancement in conventional treatments, liver cancer remains largely incurable. Nowadays, the use of naturally occurring anticancer agents particularly flavonoids is subject to more attention due to their enhanced physicochemical properties. Therefore, this study underlines the use of a natural anticancer agent taxifolin in the treatment of liver cancer using hepatocellular carcinoma cell line HepG2 and Huh7. The aim of our study is to devise a natural and efficient solution for the disease prevalent in Pakistan. The study involved the assessment of binding of ligand taxifolin using molecular docking. The binding of taxifolin with the proteins (Hif1-α, VEGF and Akt) was calculated by docking using Vina and Chimera. Further evaluation was performed by cell viability assay (MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) Assay), colony formation assay, cell migration assay, DNA ladder assay and flow cytometry. To see whether taxifolin directly affected expression levels, analysis of gene expression of Hif1-α, VEGF and Akt was performed using real-time polymerase chain reaction (qPCR) and western blotting. In silico docking experiments revealed that these proteins showed favorable docking scores with taxifolin. Treatment with taxifolin resulted in the inhibition of the liver cancer growth and migration, and induced apoptosis in HepG2 and Huh7 cell lines at an inhibitory concentration (IC50) value of 0.15 µM and 0.22 µM, respectively. The expression of HIF1-α, VEGF and Akt was significantly reduced in a dose- dependent manner. The inhibitory effect of taxifolin on hepatic cells suggested its chemopreventive and therapeutic potential. The studied compound taxifolin exhibited pronounced pro-apoptotic and hepatoprotective potential. Our study has confirmed the pro-apoptotic potential of taxifolin in liver cancer cell lines and will pave a way to the use of taxifolin as a chemotherapeutic agent after its further validation on the animal models and humans based epidemiological studies.

Dataset Information

Alpinumisoflavone against cancer pro-angiogenic targets: In silico, In vitro, and In ovo evaluation.

Background

Objectives

Methods

Results

Conclusion

Publications

Alpinumisoflavone against cancer pro-angiogenic targets: In silico, In vitro, and In ovo evaluation.

Similar Datasets

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