Abstract 3849: Triptolide reduces activity of RNA polymerase II

Abstract

Abstract Triptolide (TPL) possesses potent anticancer and anti-inflammatory effects. Our previous study demonstrated that radiation-induced pulmonary fibrosis in mice can be significantly reduced by TPL treatment (0.25 mg/kg/every 3 days for 1-3 months via intravenous injection). Treatment was associated with the reduction of a panel of inflammation molecules, as evidenced by a membrane array of 62 inflammatory molecules. We found that TPL has a high level of biointeraction with RNA polymerase II (Pol II). Pol II is a major enzyme complex responsible for the production of mRNA and could explain improved tumor response and reduced normal tissue toxicity. The mRNA of interleukin-1 beta (IL-1α), tumor necrosis factor-alpha (TNFα), IL-6, and Cox-2 were used as downstream products of Pol II. Alpha-amanitin (a specific inhibitor of Pol II) and actinomycin D (a pan Pol inhibitor) were used as positive controls. The results showed that: 1) Pol II was suppressed as early as 1 hour after TPL was added to cells; 2) TPL (effective at ng/ml levels) is more potent than α-amanitin and actinomycin D (effective at µg/ml levels) at reducing housekeeping genes L32 and S14; 3) the suppression of Pol II by TPL was dose dependent; and 4) TPL inhibited radiation-induced mRNA of IL-1α and TNFα at 3 hours after irradiation and IL-6 and Cox-2 at 8 hours after irradiation. It is unknown whether these early effects of TPL on Pol II impact either tumor response or normal tissue complications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3849. doi:1538-7445.AM2012-3849