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Note:
World Biochem 2019 & Regenerative Medicine 2019
Journal of Genetics and Molecular Biology | Volume 3
Page 55
OF EXCELLENCE
IN INTERNATIONAL
MEETINGS
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March 25-26, 2019 | Amsterdam, Netherlands
&
BIOCHEMISTRY AND ENZYMOLOGY
World Congress on
TISSUE ENGINEERING AND REGENERATIVE MEDICINE, STEM CELL RESEARCH
2
nd
Global Conference on
Joint Event on
METFORMIN EXHIBITED ANTICANCER ACTIVITY BY LOWERING CELLULAR
CHOLESTEROL CONTENT IN BREAST CANCER CELLS
Ankit Sharma
Central university of Rajasthan, India
L
iterature suggested that Metformin, a well-known anti-diabetic drug, showed anticancer activity in various
cancer types. Few clinical studies documented the low serum cholesterol and low TAG level in Metformin
treated patients. Literature also indicated an existence of positive association between high cholesterol and
cancer. This study aimed to find out a molecular mechanism involved in Metformin-inhibited cell growth and
metastasis in breast cancer cells. Tumor sample based clinical study found the higher expressions of cellular
cholesterol regulatory genes (e.g. HMGCoR, LDLR) in malignant breast cancer tissues as compared to benign
tissues. Our cell culture study found that treatment of breast cancer MDA-MB-231 cells with Metformin de-
creased cellular cholesterol level with concomitant inhibition of various genes (e.g. SREBF1 and LDLR) which
maintain the homeostasis of cellular cholesterol. Cell culture based experimental study documented that
Metformin inhibited cell proliferation, migration, and colony and spheroid formation of metastatic breast
cancer MDA-MB-231 cells. As a mechanism it was identified by RT-PCR that Metformin treatment inhibited
anti-apoptotic markers (Bcl2, BCLxl) and mesenchymal marker genes (Vimentin, N-cadherin) transcript levels
with simultaneous enhancement of apoptotic markers (Caspase3, Bax) and epithelial marker genes E-cadherin
and Keratin19, indicated an inhibitory effect of Metformin in proliferation and EMT of breast cancer cells. Less
number of colony and spheroid formation has been observed in Metformin treated breast cancer cells. RT-PCR
analysis also found that Metformin treatment inhibited stemness marker CD44 and BMI-1 in metastatic breast
cancer MDA-MB-231 cells. Our TRAP assay data showed that Metformin treatment inhibits breast cancer in-
duced osteolytic activity, which further inhibits the osteolytic bone metastasis. Moreover, Metformin-inhibited
cancer cell proliferation and migration was reversed by the exogenous treatment of cholesterol. Similarly, cho-
lesterol treatment reversed the Metformin-inhibited Bcl2, Vimentin, BMI-1 expression. Moreover, zymography
data documented that cholesterol treatment upregulated Metformin-inhibited MMP activity. Further, results
showed that cholesterol depletion by MBCD (Methyl B- Cyclo Dextrin), a cholesterol depleting agent inhibited
proliferation, migration and stemness in breast cancer cells. This study suggests a new molecular mechanism
where Metformin inhibits proliferation, EMT, stemness and osteolytic bone metastasis of breast cancer cells
presumably by lowering cellular cholesterol level”.
J Genet Mol Biol 2019, Volume 3