Plumbagin Attenuates the Migratory and Clonogenic Potential of Lung Cancer Cells: Utilizing Molecular Simulations to Obtain Mechanistic Insights

Lung cancer stands as a prominent contributor to cancer-linked fatalities, contributing in the highest mortality rate. Within the lung cancers, non-small cell lung cancer is more prominent. Protein kinases have important roles in metabolism, cell signaling, survival, proliferation and migration. When these kinases malfunction and become overly active, it contributes to tumor development and spread. Akt activation, involved in various cancers, fuels the cancer progression and makes tumors more resistant to treatment. Hence, targeting Akt is a promising strategy in the management of lung cancer. The effect of plumbagin in A549 cell lines is investigated in this study. The cell viability assay established the IC[Formula: see text] values as 15 [Formula: see text]M and plumbagin-induced dose-dependent decrease in the cell viability. Plumbagin attenuated the clonogenic and migratory potential of these cells and it also decreased the expression levels of pAkt, suggesting that plumbagin targets Akt phosphorylation. Molecular dynamics simulation studies revealed that plumbagin has strong affinity toward Akt1 and forms a stable complex. The binding of plumbagin to Akt1 did not alter the secondary structure of Akt1 and also induced a negligible flexibly. Inhibition of Akt/Erk pathway could be a possible mechanism of action of plumbagin for the targeting of lung cancer cells. Further study is needed in mouse and other suitable models to confirm the in vivo efficacy of plumbagin in management of lung cancer by targeting Akt1.