Gambogenic acid exerts anticancer effects in cisplatin‑resistant non‑small cell lung cancer cells
Dao-fu Shen, Yu Wang, Hongmei Niu, Chunying Liu
Abstract
Non‑small cell lung cancer (NSCLC) is the most common type of lung cancer and the most common cause of mortality in patients with lung cancer. The efficacy of cisplatin‑based chemotherapy in NSCLC is limited by drug resistance, therefore, the development of novel anticancer agents is required to overcome cisplatin resistance. The present study investigated the anticancer activity of gambogenic acid (GNA), derived from gamboge, in the cisplatin‑resistant NSCLC cell line A549/Cis. GNA was revealed to have a potent inhibitory effect on cell growth in A549/Cis cells by blocking the cell cycle and inducing apoptosis. The investigation of the molecular mechanisms identified that GNA arrested the cell cycle at the G1 phase through the downregulation of cyclin Ds, cyclin dependent kinase (CDK)4 and CDK6, and the upregulation of p53 and p21. In addition, GNA induced apoptosis by increasing the activation of caspase 3 and caspase 7, in addition to the cleavage of poly(ADP‑ribose) polymerase. The results of the present study supported the potential application of GNA in cisplatin‑resistant NSCLC.