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Phloretin Inhibits the Human Prostate Cancer Cells Through the Generation of Reactive Oxygen Species

Authors
  • Kim, Ukjin1
  • Kim, C-Yoon2
  • Lee, Ji Min1
  • Oh, Hanseul1, 3
  • Ryu, Bokyeong1
  • Kim, Jin1
  • Park, Jae-Hak1
  • 1 Seoul National University, Seoul, 08826, Republic of Korea , Seoul (South Korea)
  • 2 Konkuk University, Seoul, 05029, Republic of Korea , Seoul (South Korea)
  • 3 Korea Research Institute of Bioscience and Biotechnology, Cheongju, Chungcheongbuk, Republic of Korea , Cheongju (South Korea)
Type
Published Article
Journal
Pathology & Oncology Research
Publisher
Springer-Verlag
Publication Date
Apr 01, 2019
Volume
26
Issue
2
Pages
977–984
Identifiers
DOI: 10.1007/s12253-019-00643-y
Source
Springer Nature
Keywords
License
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Abstract

Phloretin is a flavonoid with known anticancer activities. However, we do not fully understand how phloretin mitigates prostate cancer on the molecular level. In the present study, we examined changes in proliferation, colony formation, and migration after phloretin treatment in human prostate cancer cells PC3 and DU145. We measured reactive oxygen species (ROS) and gene expression. Phloretin increased ROS and suppressed cell proliferation, migration, and colony formation in both cell lines. Additionally, phloretin treatment increased oxidative stress, as demonstrated through lower antioxidant enzymes (catalase, SOD2, Gpx1, Gpx3). In addition, their regulator CISD2 decreased in expression. We also found that increased ROS significantly downregulated multiple components of the Wnt/β-catenin signaling pathway (β-catenin, TCF4, FoxA2, c-Myc) and Twist1. Thus, anticancer activity of phloretin against human prostate cancer cells occurs through generating ROS to influence Wnt/β-catenin signaling. The results of this study suggest that phloretin has a therapeutic effect on prostate cancer in vitro, inhibiting the proliferation and migration of cancer cell lines PC3 and DU145. The mechanism of phloretin appears to be increasing ROS production. We thus recommend phloretin as a promising anticancer therapeutic agent.

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