2000 ASCB Annual Meeting Press Book - page 9

Broccoli and Cancer: the
Smoking Floret
Your mother was right. Eating broccoli is good for you
but until now we didn’t know exactly why. Studies have
shown that eating more broccoli and other brassica vegeta-
bles is linked to lower rates of cancer. A mother’s wisdom
aside, scientists have been trying to understand how broc-
coli works its magic at the cellular level. One promising
anti-cancer agent that naturally occurs in these vegetables
is indole-3-carbinol (I3C). In the stomach, I3C is rapidly
converted into its derivatives. The most important known
derivative is 3,3’-diindolylmethane (DIM). DIM is a very
active anti-cancer agent, but its intracellular targets and
mechanism of action were unknown.
Now three scientists at UC Berkeley, Chibo Hong, Gary
Firestone, and Leonard Bjeldanes, have discovered how
DIM works the broccoli effect. Using MCF-7 human breast
cancer cells, these scientists found that DIM has multiple
effects on the pathways that control cell growth and apop-
tosis. Apoptosis, or programmed cell death, is a natural
process that our bodies use to get rid of old, damaged, or
disobedient cells, including tumor cells.
The key new finding is that DIM inhibits cell growth
and DNA synthesis, which are both essential for cell divi-
sion. Importantly, DIM also promotes apoptosis in two
ways: by increasing the level of a death-promoting protein
named Bax, and by decreasing the level of an anti-death
protein named Bcl-2, which binds to and inhibits Bax.
Tumor cells often express increased levels of Bcl-2, thus
avoiding the death pathway. The Berkeley scientists
found that tumor cells treated with DIM contained less Bcl-
2 protein, and more of the pro-death Bax in its free active
form. Treatment with DIM also caused increases in mes-
senger RNAs that produce two other proteins that subdue
growth and increase cell death. Now it’s back to the lab
bench (and the vegetable aisle) to further explore the
potential cancer therapeutic and protective effects of DIM.
4
40th Annual Meeting
December 9-13, 2000
Moscone Convention Center, San Francisco
Contact:
Chibo Hong
#50 Morgan Hall
Nutritional Sciences and Toxicology
University of California at Berkeley
Berkeley, CA 94720
Phone: 510 642-0862
3,3’-Diindolylmethane (DIM), a dietary indole,
has multiple cell suppressive effect on MCF-7,
human breast cancer cells
Authors:
Chibo Hong, Gary L. Firestone* and Leonard
F. Bjeldanes
Dept. of Nutritional Sciences and Toxicology
*Dept. of Molecular Cell Biology
University of California at Berkeley, CA 94720
In an apoptosis specific assay,Annexin V assay,to detect phosphatidylserine (PS)
externalization showed:
In cotnrol group(DMSO):basically no FITC (green) nor propidium iodide(red) staining;
In DIM treated groups:there were some 'halo' images with FITC staining indicating
early stage of apoptosis,also there were some cells stained with propidium iodide (PI)
in their nuclei indicating late stage of apoptosis.
In the positive control group (Etoposide):there were cells at both early and late stages
of apoptosis
Overlay
FITC Staining
PI Staining
DMSO Control:
DIM,50
µ
M:
(3 hrs)
DIM,100
µ
M:
(10 min)
Etoposide,10
µ
M:
( 3 hrs)
At The ASCB Meeting
Poster Session Halls A/B/C
P8 - Cell Cycle Checkpoints
Author Presents
Sunday, December 10, 12:00 PM-1:30 PM
Program # 199
Board # A157
2474pPressBookrev 12/5/2000 18:35 Page 4
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