Anti-cancer effect of danshen and dihydroisotanshinone I on prostate cancer: targeting the crosstalk between macrophages and cancer cells via inhibition of the STAT3/CCL2 signaling pathway

• Published in: Oncotarget 2017-06, Vol.8 (25), p.40246-40263
• Main Authors: Wu, Ching-Yuan, Yang, Yao-Hsu, Lin, Yin-Yin, Kuan, Feng-Che, Lin, Yu-Shin, Lin, Wei-Yu, Tsai, Ming-Yen, Yang, Jia-Jing, Cheng, Yu-Ching, Shu, Li-Hsin, Lu, Ming-Chu, Chen, Yun-Ju, Lee, Kuan-Der, Kang, Hong-Yo
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Cell Movement - drug effects; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - metabolism; Coculture Techniques; Drugs, Chinese Herbal - pharmacology; Humans; Macrophages - drug effects; Macrophages - metabolism; Male; Medicine, Chinese Traditional; Mice; Phenanthrenes - pharmacology; Prostate - pathology; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Protein Transport - drug effects; Research Paper; rhoA GTP-Binding Protein - biosynthesis; Salvia miltiorrhiza - chemistry; Snail Family Transcription Factors - biosynthesis; STAT3 Transcription Factor - metabolism; Treatment Outcome
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.14958

Danshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. In our study, the in vivo protective effect of danshen in prostate cancer patients was validated through data from the National Health Insurance Research Database in Taiwan. In vitro, we discovered that dihydroisotanshinone I (DT), a bioactive compound present in danshen, can inhibit the migration of both androgen-dependent and androgen-independent prostate cancer cells. In addition, we noted that DT substantially inhibited the migratory ability of prostate cancer cells in both a macrophage-conditioned medium and macrophage/prostate cancer coculture medium. Mechanistically, DT both diminished the ability of prostate cancer cells to recruit macrophages and reduced the secretion of chemokine (C-C motif) ligand 2 (CCL2) from both macrophages and prostate cancer cells in a dose-dependent manner. Moreover, DT inhibited the protein expression of p-STAT3 and decreased the translocation of STAT3 into nuclear chromatin. DT also suppressed the expression of tumor epithelial-mesenchymal transition genes, including RhoA and SNAI1. In conclusion, danshen can prolong the survival rate of prostate cancer patients in Taiwan. Furthermore, DT can inhibit the migration of prostate cancer cells by interrupting the crosstalk between prostate cancer cells and macrophages via the inhibition of the CCL2/STAT3 axis. These results may provide the basis for a new therapeutic approach toward the treatment of prostate cancer progression.