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Beta-ionone-inhibited proliferation of breast cancer cells by inhibited COX-2 activity

  • Hong-Wei Dong
  • Kai Wang
  • Xiao-Xia Chang
  • Fei-Fei Jin
  • Qi Wang
  • Xiao-Feng Jiang
  • Jia-Ren LiuEmail author
  • Yong-Hui WuEmail author
  • Chun YangEmail author
Genotoxicity and Carcinogenicity

Abstract

As one of the isoprenoids and widely derived from many fruits and vegetables, β-ionone (BI) has a potent inhibitory proliferation of cancer cells in vitro and in vivo. However, its exact mechanism is still uncompleted understood and needs to be further verified. Cyclooxygenase-2 (COX-2), as a potential target of cancer chemoprevention, has been played pivotal roles in proliferation of tumor cells and carcinogenesis. Thus, the objective of present study was to determine that BI inhibited the activity of COX-2 in breast cancer and related to cancer cell models. Cell proliferation, DNA synthesis, the distribution of cell cycle, apoptosis induction and the expression of P38-MAPK protein were determined in MCF-7 cells by methylene blue, 3H-thymidine (TdR) incorporation, flow cytometry, TUNEL and Western blotting assays. Quinone reductase (QR) activity was determined in murine hepatoma Hepa1c1c7 cells by enzyme-linked immunosorbent assay (ELISA). The expression of COX-2 in a phorbol-12-myristate-13-acetate (PMA)-induced cell model and mammary tumor tissues was examined by Western blotting and immunohistochemistry. The results showed that BI significantly inhibited cell proliferation and DNA synthesis, arrested the distribution of cell cycle at the S phase or decreased proteins related to cell cycle such as cyclin D1 and CDK4, induced apoptosis and increased the expression of p-P38 in MCF-7 cells. BI at low doses (< 50 μmol/L) significantly increased QR activity, decreased the expression of COX-2 protein and prostaglandin E2 (PEG2) release in cell models. In addition, BI also significantly decreased the expression of COX-2 protein in rat mammary tumor tissues. Therefore, our findings indicate that BI possesses inhibitory proliferation of breast cancer cells through down-regulation of COX-2 activity.

Keywords

β-Ionone Inhibition MCF-7 cells COX-2 activity 

Notes

Acknowledgements

This research was supported by Harbin Science and Technology Innovation Talent Research Special Fund (No. 2017RALXJ005), National Natural Science Fund (No. 30200229) and Health and Family Planning Commission Research Fund of Heilongjiang (2003-125), People’s Republic of China.

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest in this study.

Supplementary material

204_2019_2550_MOESM1_ESM.docx (174 kb)
Supplementary material 1 (DOCX 172 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Occupational Health, Public Health CollegeHarbin Medical UniversityHarbinPeople’s Republic of China
  2. 2.Department of Cardiac SurgeryThe First Affiliated Hospital of GuangZhou Medical UniversityGuangzhouPeople’s Republic of China
  3. 3.Department of Clinical LaboratoryThe Forth Affiliated Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China

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