Two speakers from Nutritional Genomics & Proteomics in Cancer Prevention, September 5, 2002 (NIH campus, Bethesda, MD)
Fazlul H. Sarkar, Ph.D., Department of Pathology, Wayne State University School of Medicine, Detroit, MI spoke on “Translocation of Bax to Mitochondria Induces Apoptotic Cell Death in Indole-3-Carbinol (I3C) Treated Breast Cancer Cells”.
From the abstract:
“Indole-3-carbinol (I3C), a natural component of Brassica vegetables, has been found to be a promising cancer preventive agent. However, the precise molecular mechanism(s) through which I3C exerts its inhibitory effects on cancer cells has not been fully elucidated. We investigated the molecular mechanism(s) of action of I3C during apoptotic processes in breast epithelial cells.
Nontumorigenic and tumorigenic breast epithelial cells were exposed to I3C, and growth inhibition, apoptosis and expression of genes involved in apoptotic processes were measured. Translocation of Bax to the mitochondria was assessed by confocal imaging. Mitochondrial potential and cytochrome c release also were measured.
We found that I3C inhibits the growth of breast cancer cells with G1 arrest and induced apoptosis in these cells, concomitant with upregulation of p21 WAF1 and Bax, and downregulation of Bcl-2, Bcl-xl and Bax. I3C induces translocation of Bax to the mitochondria in both tumorigenic and nontumorigenic cells, but concomitant loss of mitochondrial potential, release of cytochrome c, and induction of apoptosis was observed only in cancer cells.
I3C exerts its effects by regulating cell cycles and by altering the expression of genes involved in apoptotic pathways. The translocation of Bax to the mitochondria alone was not sufficient during I3C-induced apoptosis. Translocation of Bax followed by mitochondrial depolarization and cytochrome c release was necessary, which may be responsible for selective induction of apoptosis in cancer cells, supporting the potential preventive and/or therapeutic benefit of I3C against cancers.”
Dr. Sarkar discussed the need for studies in cancer patients and said they will be doing some. He felt that epidemiological studies suggest that I3C may be responsible (in part) for the lower breast cancer incidence in Asians. He also said it acted in more than one way.
He stated that there had been significant progress using I3C with head/neck cancers.
Ann’s NOTE: Vitamin A analogues have also been used in head/neck as has PDT (photodynamic therapy). In private conversation with Dr. Sarkar (someone I met during my stint as a DOD reviewer), he said he thought I3C would function as well or better than Tamoxifen.
Gary Firestone, Ph.D., Department of Molecular and Cell Biology, University of California at Berkeley, “Indole-3-carbinol Signaling Controls Cell Cycle Gene Transcription in Human MCF-7 Breast Cancer Cells by Regulating Promoter-Sp1 Transcription Factor Interactions”.
From the abstract:
“Indole-3-carbinol (I3C), a compound naturally occurring in Brassica vegetables such as cabbage and broccoli, can induce a G1 cell cycle arrest of human MCF-7 breast cancer cells that is accompanies by the selective inhibition of cyclin dependent kinase 6 (CDK6) expression and stimulation of p21 (Waf1/Cip1) gene expression…
In indole treated cells, a fraction of [3H]I3C was converted into its natural diindole product, [3H]DIM, which accumulated in the nucleus, suggesting that DIM may have a role in the transcriptional activities of I3C.”
Dr. Firestone spoke about the synergy between estrogen and I3C. He suggested that I3C virtually blocks the ‘s’ phase.
From the abstract:
“Indole-3-carbinol (I3C), a natural component of Brassica vegetables, has been found to be a promising cancer preventive agent. However, the precise molecular mechanism(s) through which I3C exerts its inhibitory effects on cancer cells has not been fully elucidated. We investigated the molecular mechanism(s) of action of I3C during apoptotic processes in breast epithelial cells.
Nontumorigenic and tumorigenic breast epithelial cells were exposed to I3C, and growth inhibition, apoptosis and expression of genes involved in apoptotic processes were measured. Translocation of Bax to the mitochondria was assessed by confocal imaging. Mitochondrial potential and cytochrome c release also were measured.
We found that I3C inhibits the growth of breast cancer cells with G1 arrest and induced apoptosis in these cells, concomitant with upregulation of p21 WAF1 and Bax, and downregulation of Bcl-2, Bcl-xl and Bax. I3C induces translocation of Bax to the mitochondria in both tumorigenic and nontumorigenic cells, but concomitant loss of mitochondrial potential, release of cytochrome c, and induction of apoptosis was observed only in cancer cells.
I3C exerts its effects by regulating cell cycles and by altering the expression of genes involved in apoptotic pathways. The translocation of Bax to the mitochondria alone was not sufficient during I3C-induced apoptosis. Translocation of Bax followed by mitochondrial depolarization and cytochrome c release was necessary, which may be responsible for selective induction of apoptosis in cancer cells, supporting the potential preventive and/or therapeutic benefit of I3C against cancers.”
Dr. Sarkar discussed the need for studies in cancer patients and said they will be doing some. He felt that epidemiological studies suggest that I3C may be responsible (in part) for the lower breast cancer incidence in Asians. He also said it acted in more than one way.
He stated that there had been significant progress using I3C with head/neck cancers.
Ann’s NOTE: Vitamin A analogues have also been used in head/neck as has PDT (photodynamic therapy). In private conversation with Dr. Sarkar (someone I met during my stint as a DOD reviewer), he said he thought I3C would function as well or better than Tamoxifen.
Gary Firestone, Ph.D., Department of Molecular and Cell Biology, University of California at Berkeley, “Indole-3-carbinol Signaling Controls Cell Cycle Gene Transcription in Human MCF-7 Breast Cancer Cells by Regulating Promoter-Sp1 Transcription Factor Interactions”.
From the abstract:
“Indole-3-carbinol (I3C), a compound naturally occurring in Brassica vegetables such as cabbage and broccoli, can induce a G1 cell cycle arrest of human MCF-7 breast cancer cells that is accompanies by the selective inhibition of cyclin dependent kinase 6 (CDK6) expression and stimulation of p21 (Waf1/Cip1) gene expression…
In indole treated cells, a fraction of [3H]I3C was converted into its natural diindole product, [3H]DIM, which accumulated in the nucleus, suggesting that DIM may have a role in the transcriptional activities of I3C.”
Dr. Firestone spoke about the synergy between estrogen and I3C. He suggested that I3C virtually blocks the ‘s’ phase.
