Abstract 5682: Tanshinones in Salvia miltiorrhiza as potential chemopreventive agents against lung cancer

Abstract

Abstract The search for effective regimens with minimal adverse effects for the prevention and treatment of lung cancer remains the top priority research to eradicate this devastating disease. Several essential components determine the opportunity of success in identifying the candidate compounds, which include enhanced tissue levels, preferably in lungs after administration, safety use profiles, and more importantly preclinical evidence that is derived from clinically relevant in vivo systems. A Chinese herb medicine Salvia miltiorrhiza (Danshen) has been widely used for centuries for treatment of cardiovascular diseases without reported side effects to healthy humans. After oral administration, tanshinones are preferably accumulated at the highest levels in lungs. Several Danshen compounds, such as tanshinone IIA (T2A), tanshinone I (T1) and cryptotanshinone (CT), have also been reported to have potent activities in vitro against several cancer types including lung cancer. These promising findings strongly support that tanshinones may have potent anti-cancer, especially anti-lung cancer activities. The long-term goal of this research is to develop tanshinones as effective and safe agents for the prevention and treatment of lung cancer. We first evaluated the effects of tanshinones on the growth inhibition of lung cancer cell lines in vitro. All three tanshinones showed dose-dependent inhibition to the growth of human (H1299, H23, and A549) and murine (LLC) lung cancer cell lines at low μM ranges with T1 the most potent. Interestingly, LLC, which is usually resistant to drug treatment, was the most sensitive cell line to T1 treatment (IC50 at 3μM), but it was insensitive to T2A treatment. Cell cycle analysis showed that CT and T1 arrested cells (H1299) at S phase, whereas T2A arrested cells at G2/M phase. The growth inhibition and cell cycle arrest activities of tanshinones were associated with downregulation of cdc2 and Aurora A expression. Because T1 showed the most potent activity, we are evaluating its effect on the growth inhibition of lung tumors in mice and on the modulation of cellular and molecular markers. It is expected that the studies will provide experimental evidence to support the chemopreventive and/or therapeutic activities of tanshinones against lung cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5682.