Synergy of Taxol and rhein lysinate associated with the downregulation of ERK activation in lung carcinoma cells

Abstract

In previous studies we observed that rhein lysinate (RHL), a salt of rhein and lysine that is easily dissolved in water, inhibited the growth of tumor cells in breast cancer, ovarian cancer, hepatocellular carcinoma and cervical cancer. The present study aimed to investigate the effects of RHL on H460 and A549 non-small cell lung cancer (NSCLC) cells using a combination of RHL and Taxol. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to determine the growth inhibition effect of the drugs in the H460 and A549 cells. Cell apoptosis was analyzed by flow cytometry combined with fluorescein-isothiocyanate-Annexin V/propidium iodide (PI) staining. The expression levels of proteins were detected by western blotting. There was a significant reduction in the proliferation of the NSCLC cell lines treated with a combination of Taxol and RHL. The overall growth inhibition was directly correlated with apoptotic cell death. RHL potentiated Taxol-induced cell killing by reducing extracellular signal-regulated kinase (ERK) activity and increasing the levels of cleaved poly(ADP-ribose) polymerase (PARP) and caspase-3. Notably, the results for the Bcl-2 and NF-κB proteins also showed downregulation in the combined treatment group compared with the single-agent treatment and the untreated control groups. The present results showed that RHL potentiates the growth inhibition induced by Taxol in NSCLC cells and showed that this synergy may be associated with the downregulation of ERK activation.