Peruvoside, a cardiac glycoside, induces cell cycle arrest in non-small cell lung cancer (A549 cell line) and modulates PI3K/AKT/mTOR

Abstract Objectives Lung cancer constitutes a global health crisis that leads to mortality. The cellular signaling and cell cycle are disrupted in lung cancer. From time immemorial, plants have been a major source of medications. Notably, cardiac glycosides (CGs) potently bind to Na + /K + -ATPase in cardiac tissue. CGs show promising potential as anticancer activity. Peruvoside belongs to the cardiac glycosides, Peruvoside derived from Thevetia peruviana . Noteworthy, Peruvoside has shown promising interest due to its powerful effect toward several cancer types. The presented study evaluates Peruvoside’s effects on the proliferation as well as cell cycle progression of lung cancer A549 cells to validate its anticancer potential. Methods A549 cells were cultured and allocated into two groups: treated with Peruvoside and an untreated control group. Viability of A549 cells was assessed by WST-8 assay; cell cycle analysis was performed by flow cytometry; CDK6 and cyclin D1 protein expression was determined by Western blot; and real-time PCR analysis was performed to identify the expression of CHK1, CHK2, PI3K, AKT, and mTOR genes. Results Peruvoside at a concentration of 68.77 nM was associated with a notable anti-proliferative effect and the induction of an apoptotic cascade. Peruvoside induces cell cycle arrest at the G2/M phase, validated by Western blot and real-time PCR analysis, confirming that inhibition of proteins and genes related to cell cycle progression and expansion of the lung cancer, indicating that Peruvoside has antiproliferative and pro-apoptotic effects. Conclusions Within this research, the data showed the arrest of the cell cycle and the inhibition of the proliferation regulatory gene by Peruvoside were associated with suppression of lung cancer survival, proliferation, metastatic dissemination, and promotion of cell death.