Inhibition of Estrogen-induced Growth of Breast Cancer by Targeting Mitochondrial Oxidants
Abstract
We have completed all proposed research, except a part of Task 4-related to xenograft tumor experiments in nude mice. This will be completed during no-cost extension period. We observed in this study that estrogen induced redox signaling mediates proliferation and growth of MCF-7 cells exposed to estrogens. Over-expression of biological ROS scavengers (MnSOD and Catalase) or treatments of cells with chemical antioxidants, [N-acetylcysteine (NAC) and ebselen], inhibits estrogen induced expression of cell cycle genes as well as prevention of estrogen-induced growth of malignant breast epithelial cells. Also, findings of this study support ROS functioning as signal molecules in E2-induced cell transformation. These findings suggest that, in addition to the estrogen receptor activity, E2-generated mitochondrial ROS may promote susceptibility to malignant transformation as well as growth of malignant breast cancer cells. Thus our results suggest: 1) a new paradigm that estrogen-induced mitochondrial oxidants control the early stage of cell cycle progression and growth of breast cancer cells, 2) estrogen-induced mitochondrial oxidants control cell transformation and invasiveness of transformed cells; and 3) provide the basis for the discovery of novel antioxidant-based drugs or antioxidant gene therapies for the prevention and treatment of estrogen-dependent breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2009
- Accession Number
- ADA505266
Entities
People
- Brian Kunkle
- Deodutta Roy
- Quentin Felty
Organizations
- Florida International University