Inhibition of Estrogen-Induced Growth of Breast Cancer by Targeting Mitrochondrial Oxidants
Abstract
We have completed proposed research in the First Year Task (i) both antioxidants, N-acetylcysteine and ebselen, overexpression of ROS lowering genes, such as, catalase or mtSOD; and silencing of mtTFA are able to induce cell growth arrest in the presence of estrogen by analysis of the expression of early cell cycle biomarkers, cyclin D1 and PCNA and a part of Second Year Task (iii) estrogen-induced cell transformation experiments determined by: (a) Foci Formation, (b) Anchorage-independent (soft agar) cell growth showed that estrogen-induced conversion of normal cells to transformed cells is inhibited by treatment with N-acetylcysteine and ebselen, overexpression of MnSOD or catalase; or mtTFA silencing. Our study revealed: i) Inhibition of ROS formation or detoxification of ROS prevented estrogen-induced DNA synthesis. ii). Both antoxidant treatment and detoxification of ROS prevented E2-induced expression of cyclin D1 and pcna. iii) E2 dependent anchorage-independent growth of MCF-10A cells is dependent on ROS and is prevented by overexpression of MnSOD, catalase, or mtTFA silencing. These findings suggest that, in addition to the receptor activity of estrogens, other factor(s) are involved in the stimulation of cell growth by estrogen. Our data suggest that estrogen regulates cell cycle genes through ROS. In addition to, existing antiestrogens and antiaromatse inhibitors, validation of our novel concept that defines estrogen-induced mtROS-dependent signaling pathways that distinguish between cell transformation and tumor cell growth will help to develop antioxidant-based drug or gene therapies for the prevention and treatment of estrogen-dependent breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA475741
Entities
People
- Brian Kunke
- Deodutta Roy
- Quentin Felty
Organizations
- Florida International University