Anti-angiogenic, apoptotic and matrix metalloproteinase inhibitory activity of Withania somnifera (ashwagandha) on lung adenocarcinoma cells

Sajida; Ashwini Prabhu

doi:10.1016/j.phymed.2021.153639

Anti-angiogenic, apoptotic and matrix metalloproteinase inhibitory activity of Withania somnifera (ashwagandha) on lung adenocarcinoma cells

Phytomedicine. 2021 Sep:90:153639. doi: 10.1016/j.phymed.2021.153639. Epub 2021 Jun 30.

Authors

Sajida¹, Ashwini Prabhu²

Affiliations

¹ Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore 575018, India.
² Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore 575018, India. Electronic address: ashwinibiosciences@gmail.com.

PMID: 34280829
DOI: 10.1016/j.phymed.2021.153639

Abstract

Introduction: Withania somnifera belongs to the family Solanaceae, known as Queen of medicinal plants for its enormous use in the medicinal field. Traditionally ashwagandha is used to treat several neurological disorders. This study evaluates the cytotoxic, apoptotic, antiangiogenic and matrix metalloproteinase (MMP) inhibitory activity of W. somnifera on lung adenocarcinoma.

Methodology: Aqueous and ethanolic extracts were prepared from the roots of the W. somnifera. Qualitative and quantitative phytochemical analyses were performed using the standard protocols. Cytotoxicity was assessed using MTT assay. Further experiments were carried out with IC₅₀ concentration of the extract. Apoptosis and DNA damage were evaluated using AO-EB dual staining, Hoechst staining and Comet assay. Effect of the extract on cell migration was evaluated using scratch assay. Angiogenesis inhibition was evaluated using in ovo CAM assay and angiogenic pathway alterations were evaluated using qRT-PCR and western blotting. Autophagy induction was studied via western blotting.

Results: In this study, we found antioxidant activity and the presence of certain secondary metabolites in the ethanolic extracts. The extract showed cytotoxic activity on lung adenocarcinoma cells with an IC₅₀ of 99.7 μg/ml. The extract showed significant anti-angiogenic, apoptotic and autophagy induction activity. W. somnifera extract induced significant decrease in the cell migration at lower concentrations indicating the anti-migratory potential.

Conclusion: Our investigation revealed ethanolic extract of W. somnifera possess significant anti-angiogenic and MMP inhibitory activity and helps in inhibiting the lung adenocarcinoma cells proliferation. Further, our study revealed that the enhanced autophagy induction and apoptotic effects of W. somnifera are responsible for the potential anticancer activity of the extract.

Keywords: Angiogenesis; Cytotoxicity; Lung adenocarcinoma; Phytochemicals; Withania somnifera.

MeSH terms

A549 Cells
Adenocarcinoma of Lung* / drug therapy
Angiogenesis Inhibitors / pharmacology*
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Humans
Matrix Metalloproteinase Inhibitors / pharmacology*
Matrix Metalloproteinases
Plant Extracts* / pharmacology
Plant Roots / chemistry
Withania* / chemistry

Substances

Angiogenesis Inhibitors
Antineoplastic Agents, Phytogenic
Matrix Metalloproteinase Inhibitors
Plant Extracts
Matrix Metalloproteinases
Ashwagandha