Chemotherapeutic Activity of Purvalanol A in Lung Cancer Induced by Benzo[α]pyrene by Modulation of the MEK/CDK2/PTEN Transduction Pathway

Background: Lung carcinoma is indeed the most frequently diagnosed carcinoma glob-ally. It has a significant incident rate and is one of the leading causes of cancer-related deaths. Our study investigated the chemotherapeutic activity of purvalanol A against lung cancer. Materials and Methods: The in-vitro chemotherapeutic activity of purvalanol A was assessed in A549 cells through cell viability and flow cytometry assays. The toxicity study was carried out for the determination of LD50, and subsequently, chemotherapeutic doses of purvalanol A were evalu-ated. In this study, lung carcinoma was induced in mice by 100 mg/kg benzo[α]pyrene in 0.2 ml corn oil single i.p injection and sustained for 24 weeks. Lung carcinoma development and chemotherapeu-tic activity of purvalanol A were evaluated in mice lung tissues via the histological study, immuno-histochemistry study, cell proliferation study, and apoptotic assay via the TUNEL method. Results: The IC50 value of purvalanol A in the A549 cell line was found to be 4 μg/ml, which demon-strated a significant induction of apoptotic events dose-dependently. The percentage of apoptotic cells in A549 cell lines was determined to be 11.56%, 13.78%, 35.54%, and 57.89% following treatment with purvalanol A at concentrations corresponding to untreated, IC25, IC50, and IC75, respectively. A substantial population of caspase-3-labeled cells was detected in the M2 quadrant following the treatment with purvalanol A. In the toxicity study, LD50 of purvalanol A was found to be 5 mg/kg body weight in an acute toxicity study, and it was selected as the chemotherapeutic dose. Furthermore, the treatment with purvalanol A caused a reduction in hyperplastic abrasions of lung tissues and reestablished the typical architecture of lung tissues. Additionally, purvalanol A therapy also caused the downregulation of carcinogenic markers MEK and CDK2 expression with upregulation of PTEN expression in lung tissues. Conclusion: The progression of lung carcinoma was markedly decreased by the induction of apop-tosis and abrogation of cancer cell progression, providing insights for the development of a suitable molecular mechanism for purvalanol A-mediated chemotherapy against lung cancer. result: The IC50 value of purvalanol A in A549 cell line has been found to be 4 µg/ml which demonstrate a significant induction of apoptotic event dose dependently. Furthermore, the treatment with purvalanol A causes the reduction of hyperplastic abrasions of lung tissues and reestablished the typical architecture of lung tissues. Additionally, purvalanol A therapy also causes the downregulation of carcinogenic markers MEK and CDK2 expression with upregulation of PTEN expression in lung tissue.