Synergistic anti-proliferative and pro-apoptotic activities of 5F and cisplatin in human non-small cell lung cancer NCI-H23 cells

Two-drug combination chemotherapy, often including cisplatin and one other drug, remains the standard of care for patients with advanced non-small cell lung cancer (NSCLC). To improve the treatment of late-stage NSCLC and decrease the toxicity of combination chemotherapy, the search for novel drugs remains vigorous. Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (5F), a bioactive compound isolated from the herb Pteris semipinnata L., has previously been shown to induce apoptosis and inhibit proliferation in various cancer cells. One outstanding property of 5F is its minimal side effects. In the present study, 5F was combined with cisplatin to treat NCI-H23 cells; proliferation, apoptosis and cell cycle arrest were measured by an MTT assay, Annexin V staining/flow cytometry and propidium iodide staining/flow cytometry, respectively. The messenger RNA levels of β-catenin, glycogen synthase kinase (GSK)-3β, c-Myc and cyclin D1 were determined by reverse transcription-quantitative polymerase chain reaction, and the protein levels of β-catenin and GSK-3β were measured by western blot analysis. The results revealed that 5F and cisplatin synergistically induced apoptosis and inhibited cell growth, arrested cell cycles in the G0/G1 phase, downregulated β-catenin, c-Myc and cyclin D1, and upregulated GSK-3β. These findings merit in vivo studies using animal models of NSCLC to confirm the addition of 5F as a third drug to cisplatin-based combination therapy for late-stage NSCLC.