Inhibition of Estrogen-Induced Growth of Breast Cancer by Targeting Mitochondria 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 estrogeninduced mitochondrial oxidants control the early stage of cell cycle progression and growth of breast cancer cells, 2) estrogeninduced 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 estrogendependent breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2010
- Accession Number
- ADA530428
Entities
People
- Deodutta Roy
Organizations
- Florida International University