TY - JOUR
T1 - Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in nontumorigenic breast epithelial cells
AU - Wahidur Rahman, K. M.
AU - Aranha, Olivia
AU - Sarkar, Fazlul H.
N1 - Funding Information:
This project was partly funded by the George Puschelberg Foundation awarded to F. H. S. We thank Dr. Kamiar Moin and Linda Mayernik for their invaluable assistance with the confocal microscopic imaging. Supported by Center Grants P30ES06639 from the National Institutes of Environmental Health Sciences. We would like to thank Erie Van Buren, Evano Piasentin, and Dr. Stephen Lerman for their assistance in the flow cytometry core facility supported by the grant P30CA22453 from the National Cancer Institute, which supports this core facility at Wayne State University School of Medicine. Address correspondence to F. H. Sarkar, Department of Pathology, Wayne State University School of Medicine, 9374 Scott Hall, 540 Eeast Canfield Avenue, Detroit, MI 48201. Phone: 313–966–7279. FAX: 313–966–7558 or 313–577-0057. E-mail: fsarkar@med.wayne.edu.
PY - 2003
Y1 - 2003
N2 - Recent results from epidemiology, in vitro cell culture and in vivo (animal and human) studies have suggested the benefits of indole-3-carbinol (I3C) for the prevention of many types of cancer, including breast cancer. However, there are no reports, to the best of our knowledge, on the effect of I3C on isogenic nontumorigenic and tumorigenic breast epithelial cells, and there is a significant void in our understanding of the molecular mechanism(s) by which I3C induces apoptotic cell death in breast cancer cells. To fill this gap in our understanding, we conducted experiments to investigate the effects of I3C on an isogenic nontumorigenic (MCF10A) and tumorigenic (MCF10CA1a [CA1a]) breast epithelial cells. Here we show that CA1a cells are more sensitive to low concentration of I3C in terms of cell growth inhibition compared to MCF10A cells. We further report that I3C upregulates Bax/Bcl-2 ratio and downregulates Bcl-xL expression in CA1a cells but not in MCF10A cells. We also report, for the first time, that I3C induces Bax translocation to the mitochondria, causing mitochondrial depolarization, resulting in the loss of mitochondrial potential leading to the release of cytochrome c and subsequent cell death in CA1a cells but not in MCF10A cells. From these results, we conclude that I3C selectively induces apoptosis in breast cancer cells, but not in nontumorigenic breast epithelial cells, suggesting the potential therapeutic benefit of I3C against breast cancer.
AB - Recent results from epidemiology, in vitro cell culture and in vivo (animal and human) studies have suggested the benefits of indole-3-carbinol (I3C) for the prevention of many types of cancer, including breast cancer. However, there are no reports, to the best of our knowledge, on the effect of I3C on isogenic nontumorigenic and tumorigenic breast epithelial cells, and there is a significant void in our understanding of the molecular mechanism(s) by which I3C induces apoptotic cell death in breast cancer cells. To fill this gap in our understanding, we conducted experiments to investigate the effects of I3C on an isogenic nontumorigenic (MCF10A) and tumorigenic (MCF10CA1a [CA1a]) breast epithelial cells. Here we show that CA1a cells are more sensitive to low concentration of I3C in terms of cell growth inhibition compared to MCF10A cells. We further report that I3C upregulates Bax/Bcl-2 ratio and downregulates Bcl-xL expression in CA1a cells but not in MCF10A cells. We also report, for the first time, that I3C induces Bax translocation to the mitochondria, causing mitochondrial depolarization, resulting in the loss of mitochondrial potential leading to the release of cytochrome c and subsequent cell death in CA1a cells but not in MCF10A cells. From these results, we conclude that I3C selectively induces apoptosis in breast cancer cells, but not in nontumorigenic breast epithelial cells, suggesting the potential therapeutic benefit of I3C against breast cancer.
UR - http://www.scopus.com/inward/record.url?scp=0037971286&partnerID=8YFLogxK
U2 - 10.1207/s15327914nc4501_12
DO - 10.1207/s15327914nc4501_12
M3 - Article
C2 - 12791510
AN - SCOPUS:0037971286
VL - 45
SP - 101
EP - 112
JO - Nutrition and Cancer
JF - Nutrition and Cancer
SN - 0163-5581
IS - 1
ER -