Page 65
allied
academies
Cell Science, Stem Cell Research &
Pharmacological Regenerative Medicine
November 29-30, 2017 | Atlanta, USA
Annual Congress on
Adv cel sci tissue cul 2017 | Volume 1 Issue 2
M
etformin, a type II diabetic treatment drug, which
inhibits transcription of gluconeogenesis genes, has
recently been shown to lower the risk of some diabetes-
related tumors, including breast cancer. Recently, cancer
stem cells have been demonstrated to sustain the growth of
tumors and are resistant to therapy. To test the hypothesis
that metformin might be reducing the risk to breast cancers,
the human breast carcinoma cell line, MCF-7, grown in
3-dimensional mammospheres which represent human
breast cancer stem cell population, were treated with
various known and suspected breast cancer chemicals with
and without non-cytotoxic concentrations of metformin.
Using
OCT4
expression as a marker for the cancer stem cells,
the number and size were measured in these cells. Results
demonstrated that TCDD (100 nM) and bisphenol A (10 mM)
increased the number and size of the mammospheres, as did
estrogen (10 nME2). Bymonitoring a cancer stemcell marker,
OCT4
, the stimulation by these chemicals was correlated
with the increased expression of
OCT4
. On the other hand,
metformin at 1 and 10 mM concentration dramatically
reduced the size and number of mammospheres. Results
also demonstrated the metformin reduced the expression of
OCT4
in E2 & TCDD mammospheres but not in the bisphenol
A mammospheres, suggesting different mechanisms of
action of the bisphenol A on human breast carcinoma cells.
In addition, these results support the use of 3-dimensional
human breast cancer stem cells to screen for potential
human breast tumor promoters and breast chemopreventive
and chemotherapeutic agents.
e:
James.Trosko@hc.msu.eduMetformin represses self-renewal of the human breast carcinoma stem cells via inhibition of estrogen
receptor-mediated
OCT4
expression
James E Trosko
1, 2
, Ji-Won Jung
1
, Sang-Bum Park
1
, Soo-Jin Lee
1
, Min-Soo Seo
1
and
Kyung-Sun Kang
1
1
Seoul National University, Republic of Korea
2
Michigan State University, USA