Article Text

Download PDFPDF
Redox-Active Iron-Induced Oxidative Stress in the Pathogenesis of Clear Cell Carcinoma of the Ovary
  1. Yoshihiko Yamada, MD, PhD,
  2. Hiroshi Shigetomi, MD,
  3. Akira Onogi, MD,
  4. Shoji Haruta, MD, PhD,
  5. Ryuji Kawaguchi, MD, PhD,
  6. Shozo Yoshida, MD, PhD,
  7. Naoto Furukawa, MD, PhD,
  8. Akira Nagai, MD,
  9. Yasuhito Tanase, MD, PhD,
  10. Taihei Tsunemi, MD,
  11. Hidekazu Oi, MD, PhD and
  12. Hiroshi Kobayashi, MD, PhD
  1. Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
  1. Address correspondence and reprint requests to Hiroshi Kobayashi, MD, PhD, Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. E-mail: hirokoba{at}


Objective: Epithelial ovarian cancer (EOC) is the most lethal pelvic gynecologic cancer. Clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) of the ovary have been associated with endometriosis, thus indicating that endometriosis has been believed to increase the risk of developing EOC. The aim of our review was to identify and synthesize the most current information on CCC with regard to molecular and pathophysiological distinctions.

Method: This article reviews the English-language literature for molecular, pathogenetic, and pathophysiological studies on endometriosis and endometriosis-associated ovarian cancer (EAOC). In this review, we focus on the functions and roles of redox-active iron in CCC carcinogenesis.

Results: The iron-induced reactive oxygen species signals can contribute to carcinogenesis via 3 major processes: step 1, by increasing oxidative stress, which promotes DNA mutagenesis, histone modification, chromatin remodeling, and gene products activation/inactivation thus contributing to EAOC initiation; step 2, by activating detoxification and antiapoptotic pathways via the transcription factor hepatocyte nuclear factor 1β overexpression, thereby contributing to CCC promotion; and step 3, by creating an environment that supports sustained growth, angiogenesis, migration, and invasion of cancer cells via estrogen-dependent (EAC) or estrogen-independent (CCC) mechanisms, thus supporting tumor progression and metastasis.

Conclusions: These aspects of reactive oxygen species biology will be discussed in the context of its relationship to EAOC carcinogenesis.

  • Ovarian cancer
  • Clear cell carcinoma
  • Oxidative stress
  • Iron
  • Redox

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • This study was supported by KAKENHI (Japan Society for the Promotion of Science Grant-in-Aid).

  • No potential conflicts of interest relevant to this article were reported.