Work

Asiatic acid impedes NSCLC progression by inhibiting COX ‐2 and modulating PI 3 K signaling

Year: 2024

Type: article

Abstract: Non-small cell lung cancer comprises up to 85% of lung cancer cases and has a poor prognosis. At present, there are still no effective treatments for this illness. Evidence suggests that the prostaglandin [cyclooxygenase-2 (COX-2)] and leukotriene [lipoxygenase-5 (5-LOX)] pathways are involved in lung cancer carcinogenesis. Therefore, novel agents that target COX-2 and 5-LOX may have therapeutic potential. In the present study, we examined the role of asiatic acid (AA), a triterpenoid saponin, in targeting the protein kinases responsible for lung cancer proliferation and mobility. The experimental data revealed that AA inhibited the growth of lung cancer cells (> 50%) and it significantly impeded the proliferation of lung cancer cells by inhibiting COX-2, which results in downregulation of the phosphotidyl inositol-3 kinase/protein kinase B/mammalian target of rapamycin signaling pathway, leading to an induction of cytotoxic autophagy-mediated apoptosis. Mechanistically, the expression of mitogen-activated protein kinase/extracellular signal-regulated kinase, hypoxia-inducible factor-1 and vascular endothelial growth factor is downregulated by AA, thereby reducing cell mobility and invasion. It also shows negative osmotic fragility on healthy human erythrocytes. It is concluded that AA may be a viable therapeutic drug for non-small cell lung cancer treatment, which opens new opportunities for synthesizing analogues.

Source: FEBS Letters

DOI: 10.1002/1873-3468.15027

Authors: Jyoti Singh, Yusuf Hussain, Abha Meena, Rohit Anthony Sinha, Suaib Luqman

Institutions: Jawaharlal Nehru University, Central Institute of Medicinal and Aromatic Plants, Academy of Scientific and Innovative Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences

Language: English

Topic: Natural product bioactivities and synthesis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funder: Central Institute of Medicinal and Aromatic Plants