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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.edu

Metformin 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