A potential target of Tanshinone IIA for acute promyelocytic leukemia revealed by inverse docking and drug repurposing.

Shao-Jun Chen

doi:10.7314/apjcp.2014.15.10.4301

Abstract

Tanshinone IIA is a pharmacologically active ingredient extracted from Danshen, a Chinese traditional medicine. Its molecular mechanisms are still unclear. The present study utilized computational approaches to uncover the potential targets of this compound. In this research, PharmMapper server was used as the inverse docking tool and the results were verified by Autodock vina in PyRx 0.8, and by DRAR-CPI, a server for drug repositioning via the chemical-protein interactome. Results showed that the retinoic acid receptor alpha (RARα), a target protein in acute promyelocytic leukemia (APL), was in the top rank, with a pharmacophore model matching well the molecular features of Tanshinone IIA. Moreover, molecular docking and drug repurposing results showed that the complex was also matched in terms of structure and chemical-protein interactions. These results indicated that RARα may be a potential target of Tanshinone IIA for APL. The study can provide useful information for further biological and biochemical research on natural compounds.

Highlights

Tanshinone IIA (Figure 1) is the most abundant active compound isolated from Danshen (Salvia miltiorrhiza), a traditional Chinese medicine, which has been used in preventing and treating cardiovascular diseases for more than 2000 years in China and other Asian countries (Gao et al, 2012; Xu et al, 2013)
PharmMapper server was used as the inverse docking tool andnd the results were verified by Autodock vina in PyRx 0.8, and by DRAR-CPI, a server for drug repositioning via the chemical-protein interactome
Results showed that the retinoic acid receptor alpha (RARα), a target protein in acute promyelocytic leukemia (APL), was in the top rank, with a pharmacophore model matching well the molecular features of Tanshinone IIA

Summary

Introduction

Tanshinone IIA (Figure 1) is the most abundant active compound isolated from Danshen (Salvia miltiorrhiza), a traditional Chinese medicine, which has been used in preventing and treating cardiovascular diseases for more than 2000 years in China and other Asian countries (Gao et al, 2012; Xu et al, 2013). The anti-tumor effect of Tanshinone IIA includes enhancing apoptosis of advanced cervix carcinoma CaSki cells (Pan et al, 2013), inhibiting invasion and metastasis of human colon carcinoma cells (Shan et al, 2009), suppressing angiogenesis in human colorectal cancer (Zhou et al, 2012), down-regulating epidermal growth factor receptors in hepatocelluar carcinoma cell (Zhai et al, 2009), and inhibiting Stat in breast cancer stem cells (Lin et al, 2013). Identifying new indications or new targets for existing drugs is an efficient way of maximizing their potential (Luo et al., 2011). Computer-aided approaches have been widely used in drug research to improve the efficiency of the drug discovery and development pipeline, depending on the purpose and systems of interest (Zhang, 2011). We reported that GTPas HRas may be a potential anticancer target of Danshensu by PharmMapper, an inverse docking approach (Chen et al, 2014). Identifying new indications or new targets for existing drugs via computer tool is becoming a new hotspot in the drug research

Objectives

Methods

Results