Bcl-2 is essential for Foeniculum vulgare seed extract-induced apoptosis in lung cancer

Abstract Background The factors behind the pathogenesis of lung cancer are not clear, and treatment failure is generally caused by drug resistance, recurrence, and metastasis. Development of new therapeutic agents to overcome drug-resistance remains a challenge clinically. Various extracts of Foeniculum vulgare have shown promising anticancer activity; however, effects on lung cancer and the underlying molecular mechanisms of action are not clear. Methods The cytotoxicity effects of EEFS were assessed by morphological changes or MTT assay. The BALB/c nude mice xenograft model was used for the in vivo study. Apoptotic ratio assay based on Annexin V-PI staining were measured by flow cytometry. Effect of EEFS on expression of apoptotic proteins was measured by Western blot. Mitochondria toxicity was evaluated by fluorescence to show membrane potential under a fluorescent microscope and Cytochrome C release. Results We found that the ethanol extract of Foeniculum vulgare seeds (EEFS) significantly reduced lung cancer cell growth in vitro and in vivo. EEFS decreased the viability of and triggered apoptosis in the lung cancer cell lines NCI-H446 and NCI-H661. EEFS induced apoptosis mainly through inhibition of Bcl-2 protein expression, reduction of mitochondrial membrane potential, and release of Cytochrome C. Moreover, EEFS significantly inhibited colony formation and cell migration in lung cancer cells. EEFS also effectively inhibited the growth of xenograft tumors derived from NCI-446 cells by reducing Bcl-2 protein expression and inducing apoptosis. Conclusions Taken together, these findings suggest that EEFS exerts anti-lung cancer activity by targeting the Bcl-2 protein and may have potential as a therapeutic drug for lung cancer.