An In Silico Analysis of Cytotoxic Effects of Peruvoside on A549 Cell Line
DOI:
https://doi.org/10.32947/ajps.v26i3.1401Keywords:
A549, cytotoxicity, genotoxicity, plant extract, PeruvosideAbstract
Background: Lung cancer is a challenging disease. Treatment strategies are effective in enhancing patient survival. Nonetheless, they possess drawbacks. The low response rate, unexpected intrinsic and acquired resistance. Therefore, there is a need for the development of novel cancer therapies that minimize harm to normal cells. Peruvoside, a cardiac glycoside derived from Thevetia Peruviana, has been utilized in this experiment for its promising anticancer effect. This study aimed to evaluate the anticancer potential of Peruvoside using integrated in silico ADME-Tox prediction and in vitro validation in A549 lung cancer cells.
Method: In vitro analysis includes the cytotoxicity assay using WST-8 on cancer and normal cells, and the genotoxicity of lung cancer cells was measured by a comet assay. In addition, in silico analysis (SwissADME and Pro-Tox 3.0) was applied to estimate the pharmacokinetic and toxicity profile of Peruvoside.
Result: The cytotoxicity assay showed that there is a significant reduction in cell viability of A549 cells with a selective cytotoxicity toward cancer cells determined by the selectivity index (SI), which was SI ≥ 10, suggesting its safety toward normal cells. The genotoxicity result showed that Peruvoside has damaged the DNA of A549 cells; in silico analysis confirms these results by categorizing Peruvoside in class 4 toxicity with an LD50 of 2000 mg/kg and estimating lack of blood-brain barrier penetration and inhibiting the CYP450 enzyme.
Conclusion: It was concluded that Peruvoside exhibits a potent cytotoxic impact on lung cancer cells while remaining harmless to normal cells. which is confirmed by DNA damage of the comet assay and the safety margin of Peruvoside with the pharmacokinetic profile of in silico analysis.
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