WASHINGTONConjugated linoleic acid (CLA) shows evidence of
inhibiting mammary carcinogenesis and angiogenesis in both animal and
in vitro models, said Margot M. Ip, PhD, professor of pharmacology
and therapeutics, Roswell Park Cancer Institute.
Conjugated linoleic acid acts in two ways, Dr. Ip said at the 10th
Annual Research Conference of the American Institute for Cancer
Research (AICR). It directly inhibits growth of mammary epithelial
cells by inhibition of DNA synthesis and stimulation of cell death.
Conjugated linoleic acid is a fatty acid found in trace amounts in
meats and dairy products; it is synthesized by bacteria in the rumen
of the source animals. Long-term studies have already shown that
feeding CLA to rats cuts mammary tumor incidence in half. Other data
indicate inhibition of skin and forestomach carcinogenesis.
In Vitro Studies
Using mammary epithelial cells from rats in culture, Dr. Ip found
that CLA (but not linoleic acid) inhibits the growth of normal
mammary epithelial cells and inhibits DNA synthesis.
Dr. Ip also observed a 3.5-fold increase in apoptosis of normal
mammary epithelial cell organoids and an inhibition of the growth
rate of mammary tumor cells.
Stromal-epithelial interactions are crucial for the normal
development of the breast, Dr. Ip said. Conjugated
linoleic acid modifies the differentiation of stromal cells and thus
indirectly affects the growth of both normal and malignant mammary
This occurs by inhibition of DNA synthesis and stimulation of
apoptosis, not through changes in activation or localization of
protein kinase C, she said.
Mammary stromal cells, she said, have stem-cell-like properties and
can be induced to form fibroblasts, adipocytes, or capillary-like
cells, depending on the hormones or growth factors in the culture
medium or whether the cells are grown on an extracellular matrix.
Conjugated linoleic acid, too, stimulates differentiation of mammary
stromal cells to adipocytes that can accumulate lipid. At the same
time, CLA inhibits in vitro vasculogenesis. Given all this, Dr. Ip
wanted to know if CLA could inhibit angiogenesis in vivo as well, and
studies to address that are currently underway.
One problem for potential human consumption of CLA is that it is
normally found in high-fat foods, Dr. Ip said, but it might be added
to low-fat dairy or other products at the processing stage.