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Isopimpinellin extends antiangiogenic effect through overexpression of miR-15b-5p and downregulating angiogenic stimulators

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Abstract

Background

Angiogenesis is the formation of new blood vessels from an existing vasculature through a series of processes such as activation, proliferation, and directed migration of endothelial cells. Angiogenesis is instrumental in the metastatic spread of tumors. Isopimpinellin, a furanocoumarin group of phytochemicals, is an anticarcinogenic agent. However, no studies have proven its antiangiogenic effects. The current study thus aimed to screen the antiangiogenic effect of isopimpinellin.

Methods and results

Human Umblical Vein Endothelial Cell (HUVEC) as an in vitro model and zebrafish embryos as an in vivo model was used in this study. The experimental results showed that isopimpinellin effectively inhibited HUVEC proliferation, invasion, migration, and tube formation, which are the key steps in angiogenesis by markedly suppressing the expression of pro-angiogenic genes VEGF, AKT, and HIF-1α. In addition, isopimpinellin exerts its anti-angiogenic effect through the regulation of miR-15b-5p and miR-542-3p. Furthermore, in zebrafish embryos, isopimpinellin inhibited the development of intersegmental vessels (ISVs) through the significant downregulation of all pro-angiogenic genes vegf, vegfr2, survivin, angpt-1, angpt-2, and tie-2.

Conclusion

Collectively, these experimental findings offer novel insights into the antiangiogenic nature of isopimpinellin and open new avenues for therapeutic approaches.

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Availability of data and material

The datasets analyzed during the study are available on request from the corresponding author.

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Acknowledgements

This study was funded and supported by the Department of Science and Technology (DST), Science and Engineering Research Board (SERB), Early Career Research (ECR) Grant (DST No.: ECR/2015/000265). The authors also thank DST-FIST, UGC-SAP and DHR-MRU for the infrastructural facility.

Funding

This work was supported by Science and Engineering Research Board (SERB), Early Career Research (ECR) Grant (DST No.: ECR/2015/000265).

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Authors and Affiliations

  1. Department of Genetics, Dr. ALM PG IBMS, University of Madras, Chennai, Tamilnadu, 600113, India

    Sambhavi Bhagavatheeswaran, Vinu Ramachandran & Anandan Balakrishnan

  2. Department of Pharmacology and Neuro Science, Texas Tech University Health Sciences, Lubbock, TX, 79430, USA

    Sambantham Shanmugam

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  1. Sambhavi Bhagavatheeswaran
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  2. Vinu Ramachandran
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  4. Anandan Balakrishnan
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Contributions

SB: conceptualization, methodology, investigation, writing—original draft. VR: conceptualization, methodology. SS: conceptualization, writing—review and editing. AB: conceptualization, supervision, writing—review and editing.

Corresponding author

Correspondence to Anandan Balakrishnan.

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The ethical clearance was granted by institutional animal ethical committee with the approval number [Approval No.: 01/36/2015].

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Bhagavatheeswaran, S., Ramachandran, V., Shanmugam, S. et al. Isopimpinellin extends antiangiogenic effect through overexpression of miR-15b-5p and downregulating angiogenic stimulators. Mol Biol Rep 49, 279–291 (2022). https://doi.org/10.1007/s11033-021-06870-4

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