Natural Prenylflavones from the Stem Bark of Artocarpus altilis : Promising Anticancer Agents for Oral Squamous Cell Carcinoma Targeting the Akt/mTOR/STAT-3 Signaling Pathway.
Maniyamma AswathyDey ParamaMangala HegdeSherin DrRavi S LankalapalliKokkuvayil Vasu RadhakrishnanAjaikumar B KunnumakkaraPublished in: ACS omega (2024)
Artonin E (AA2) and artobiloxanthone (AA3) were extracted and purified from the acetone extract of the stem bark of Artocarpus altilis (Parkinson) Fosberg. Preliminary investigations of both candidates revealed promising cytotoxic effects in oral cancer cells. Moreover, these candidates modulated the expression of pivotal proteins linked to oral cancer progression, eliciting apoptosis through caspase-3 and caspase-9 activation. Additionally, our results showed that AA2 and AA3 suppressed several proteins linked with oral cancer, such as Bcl-2, COX-2, VEGF, and MMP-9, and modulated the cell signaling pathways, such as Akt/mTOR and STAT-3, offering valuable insights into the underlying mechanism of action of these compounds. These findings were robustly validated in silico using molecular docking and molecular dynamic simulations. To our knowledge, these findings have not been previously reported, and the continued exploration and development of these natural products may offer a potential avenue for the effective management of this malignancy.
Keyphrases
- signaling pathway
- molecular docking
- cell proliferation
- induced apoptosis
- pi k akt
- cell death
- oxidative stress
- cell cycle arrest
- endoplasmic reticulum stress
- single cell
- molecular dynamics simulations
- epithelial mesenchymal transition
- poor prognosis
- healthcare
- vascular endothelial growth factor
- endothelial cells
- cell therapy
- stem cells
- cell migration
- binding protein
- cancer therapy
- anti inflammatory
- human health