Inhibition of Estrogen-induced Growth of Breast Cancer by Targeting Mitochondrial Oxidants
Abstract
We have completed proposed research of the Second Year Task (iii) and the part of Task (iv) by studying: (a) Foci Formation, (b) Anchorage-independent cell growth, and (c) tumor spheroid formation using new 3D HuBiogel bioassay whether estrogen induced conversion of normal cells to transformed cells is inhibited by treatment with antioxidants, over expression of MnSOD, catalase, PrxIII, Trx2; or mtTFA silencing. Normal breast epithelial cells respond to E2 in terms of producing ROS very similar to breast cancer cells. E2 treatment to MCF-10A cells increased the formation of ROS. Over expression of catalase or silencing of mtTFA prevented E2-induced anchorage-independent growth of MCF-10A cells. We observed similar results using 3-D culture of transformed cells. These results support ROS functioning as signal molecules in E2-induced cell transformation. These findings suggest that, in addition to the receptor activity of E2, E2-generated ROS may promote susceptibility to malignant transformation. Thus our results suggest: (1) a new paradigm that estrogen-induced oxidants control cell transformation and invasiveness of transformed cells, and (2) 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, 2008
- Accession Number
- ADA486214
Entities
People
- Brian Kunkle
- Deodutta Roy
- Quentin Felty
Organizations
- Florida International University