Dihydroisotanshinone I combined with radiation inhibits the migration ability of prostate cancer cells through DNA damage and CCL2 pathway

I. Yun Lee, Yin Yin Lin, Yao Hsu Yang, Yu Shin Lin, Chun Liang Lin, Wei Yu Lin, Yu Ching Cheng, Li Hsin Shu, Ching Yuan Wu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

12 Scopus citations

Abstract

Background: Radiotherapy plays an important role in the treatment of prostate cancer. Despite that sophisticated techniques of radiotherapy and radiation combined with chemotherapy were applied to the patients, some tumors may recur. Therefore, the study investigated the effect of dihydroisotanshinone I (DT) and the combination treatment of 5 μM DT and 5Gy irradiation (IR) against the migration ability of prostate cancer cells. Methods: DT and the combination treatment were studied for its biological activity against migration ability of prostate cancer cells with transwell migration assay. Subsequently, we tried to explore the underlying mechanism with ELISA, flow cytometry and Western's blotting assay. Results: The results showed that DT and the combination treatment substantially inhibited the migration ability of prostate cancer cells. DT and the combined treatment can decrease the ability of macrophages to recruit prostate cancer cells. Mechanistically, DT and the combination treatment reduced the secretion of chemokine (C-C Motif) Ligand 2 (CCL2) from prostate cancer cells. We also found that DT treatment induced the cell cycle of prostate cancer cells entering S phase and increased the protein expression of DNA damage response proteins (rH2AX and phosphorylated ataxia telangiectasia-mutated [ATM]) in DU145 cells and PC-3 cells. Conclusions: DT displays radiosensitization and antimigration effects in prostate cancer cells by inducing DNA damage and inhibiting CCL2 secretion. We suggest that DT can be used as a novel antimetastatic cancer drug or radiosensitizer in the armamentarium of prostate cancer management.

Original languageEnglish
Article number5
JournalBMC Pharmacology and Toxicology
Volume19
Issue number1
DOIs
StatePublished - 31 01 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s).

Keywords

  • CCL2
  • DNA damage
  • Dihydroisotanshinone I
  • Prostate cancer
  • Radiosensitive

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