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.

Abstract

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.

• Authors: Ching-Yuan Wu, Yao-Hsu Yang, Yin-Yin Lin, Feng-Che Kuan, Yu-Shin Lin, Wei-Yu Lin, Ming-Yen Tsai, Jia-Jing Yang, Yu-Ching Cheng, Li-Hsin Shu, Ming-Chu Lu, Yun-Ju Chen, Kuan-Der Lee, Hong-Yo Kang
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 25 Pg. 40246-40263 (Jun 20 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28157698 (Publication Type: Journal Article)

Chemical References

• CCL2 protein, human
• Chemokine CCL2
• Drugs, Chinese Herbal
• Phenanthrenes
• SNAI1 protein, human
• STAT3 Transcription Factor
• STAT3 protein, human
• Snail Family Transcription Factors
• RHOA protein, human
• dan-shen root extract
• dihydroisotanshinone I
• rhoA GTP-Binding Protein

Topics

• Animals
• Cell Line, Tumor
• Cell Movement (drug effects)
• Chemokine CCL2 (biosynthesis, metabolism)
• Coculture Techniques
• Drugs, Chinese Herbal (pharmacology)
• Humans
• Macrophages (drug effects, metabolism)
• Male
• Medicine, Chinese Traditional
• Mice
• Phenanthrenes (pharmacology)
• Prostate (pathology)
• Prostatic Neoplasms (drug therapy, pathology)
• Protein Transport (drug effects)
• STAT3 Transcription Factor (metabolism)
• Salvia miltiorrhiza (chemistry)
• Snail Family Transcription Factors (biosynthesis)
• Treatment Outcome
• rhoA GTP-Binding Protein (biosynthesis)