Tanshinone IIA may inhibit the growth of small cell lung cancer H146 cells by up-regulating the Bax/Bcl-2 ratio and decreasing mitochondrial membrane potential

Abstract

Tanshinone IIA (Tan-IIA) may inhibit the growth of human non-small cell lung cancer A549 cells. However, the molecular mechanisms behind this malignancy have yet to be established. In the present study, we examined the effects of Tan-IIA on human small cell lung cancer H146 cells in vitro. The cytotoxicity of Tan-IIA in H146 cells was measured using the MTT assay. Mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and Ca2+ in H146 cells were detected by flow cytometry, and the protein expression of Bax, Bcl-2, Caspase-3, NF-κBp65, GADD153 and β-actin in H146 cells was measured by Western blotting. H146 cells were inhibited in a dose-dependent manner. The protein expression of GADD153 and Caspase-3 was increased, but the proto-oncogene bcl-2 was notably decreased in H146 cells treated with Tan-IIA (5 µg/ml) for 24 h. FACS showed that Tan-IIA may increase the production of ROS and Ca2+, but decreases MMP. The results indicate that Tan-IIA is capable of inhibiting the proliferation of H146 cells. One of the molecular mechanisms behind this effect may be the induction of ROS release and the decrease in MMP caused by an increase in the Bax/Bcl-2 ratio. Another may involve endoplasmic reticulum stress caused by the release of Ca2+ and an increase in GADD153 expression followed by a decrease in Bcl-2 expression, which induces a higher ratio of Bax/Bcl-2, in turn causing a decrease in MMP and leading to an increase in Caspase-3 expression and the inhibition of H146 cells. Thus, Tan-IIA may be a promising novel chemotherapeutic agent for the treatment of human small cell lung cancer H146 cells.