||5R03CA078179-02 Interpret this number
||North Dakota State University
||Lipotrope Mediated Programmed Cell Death in Mcf7 Cells
DESCRIPTION (Applicant's Description) While long-term lipotrope (choline,
methionine, folic acid, and vitamin B-12 deficiency enhances the activity of
several hepatocarcinogens, the effect of these nutrients upon mammary cancer
is not well understood. Altered DNA methylation may contribute to the
increased development of carcinoma because of its role in gene expression.
However, DNA damage is also an early consequence of methyl depletion, and it
is an important factor contributing to cell death. We hypothesize that
lipotrope deficiency may have a significant effect on the inhibition of cell
growth and on the induction of cell death in the human breast cancer cell
line, MCF-7. The experiment will examine the response of the MCF-7 cell
line to lipotrope modification, focusing on the suppression of cell growth
mediated by lipotrope deficiency. Specific aims are 1) to confirm if growth
inhibition is induced by lipotrope deficiency in the MCF-7 cell line; 2) to
investigate if lipotrope deficiency induces DNA fragmentation with
subsequent morphological appearance of cell death (apoptosis); 3) to examine
if lipotropes mediate changes in the expression of certain genes involved in
the regulation of the cell cycle and apoptosis (bcl-2); and 4) to identify
if apoptosis induced by lipotrope deficiency is a p53-dependent or
p53-independent process. The overall goal of this study is to develop a
better understanding of the role of lipotropes in the prevention and
treatment of cancer. Data from the proposed research will establish a link
between methyl donors, cell growth and cell death, and gene expression which
will be of significance to the development of dietary components and
chemotherapeutic agents that may suppress and treat human breast cancer.
Methionine cytotoxicity in the human breast cancer cell line MCF-7.
, Park C.S.
In vitro cellular & developmental biology. Animal, 2003 Mar-Apr; 39(3-4), p. 117-9.
Lipotropes regulate bcl-2 gene expression in the human breast cancer cell line, MCF-7.
, Park C.S.
In vitro cellular & developmental biology. Animal, 2002 Apr; 38(4), p. 205-7.