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

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

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 androgendependent 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.

Original languageEnglish
Pages (from-to)40246-40263
Number of pages18
JournalOncotarget
Volume8
Issue number25
DOIs
Publication statusPublished - 2017
Externally publishedYes

Fingerprint

Salvia miltiorrhiza
Prostatic Neoplasms
Macrophages
Ligands
Neoplasms
Taiwan
dihydroisotanshinone I
Epithelial-Mesenchymal Transition
Chemokine CCL2
Chinese Traditional Medicine
National Health Programs
Conditioned Culture Medium
Coculture Techniques
Androgens
Chromatin
Survival Rate
Databases

Keywords

  • CCL2
  • Dihydroisotanshinone I
  • Prostate cancer
  • Skp2
  • STAT3

ASJC Scopus subject areas

  • Oncology

Cite this

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. / 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.

In: Oncotarget, Vol. 8, No. 25, 2017, p. 40246-40263.

Research output: Contribution to journalArticle

Wu, CY, Yang, YH, Lin, YY, Kuan, FC, Lin, YS, Lin, WY, Tsai, MY, Yang, JJ, Cheng, YC, Shu, LH, Lu, MC, Chen, YJ, Lee, KD & Kang, HY 2017, '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', Oncotarget, vol. 8, no. 25, pp. 40246-40263. https://doi.org/10.18632/oncotarget.14958
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. / 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. In: Oncotarget. 2017 ; Vol. 8, No. 25. pp. 40246-40263.
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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 androgendependent 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.",
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