Journal: Cell Death & Disease

Article Title: Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy

doi: 10.1038/cddis.2012.13

Figure Lengend Snippet: Dysregulation of AMPK/mTOR pathway in human lymphoma. Expression profile of phosphorylated form of AMPK, mTOR, as well as its downstream effectors p70S6K and 4EBP1 was assessed in human lymphoma tissue using tissue array. The melanoma tissue was served as the positive control of phosphorylated AMPK

Article Snippet: The AMPK inhibitor compound C and the autophagy inhibitor 3-methyladenine were from Merck KGaA (Darmstadt, Germany).

Techniques: Expressing, Positive Control

Journal: Cell Death & Disease

Article Title: Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy

doi: 10.1038/cddis.2012.13

Figure Lengend Snippet: The inhibitory effect of metformin on growth of human lymphoma cell lines. ( a ) IC 50 results obtained from MTT assay in a series of B- and T-lymphoma cell lines after metformin treatment. ( b and c ) Response curves ( b ) and AMPK/ACC expression detected by western blot ( c ) in malignant B and T cells treated with metformin. ( d ) Metformin inhibited growth of primary lymphoma cells. ( e ) The proliferation of CD34+ cells enriched from cord blood samples was not altered by metformin up to 120 mM

Article Snippet: The AMPK inhibitor compound C and the autophagy inhibitor 3-methyladenine were from Merck KGaA (Darmstadt, Germany).

Techniques: MTT Assay, Expressing, Western Blot

Journal: Cell Death & Disease

Article Title: Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy

doi: 10.1038/cddis.2012.13

Figure Lengend Snippet: Metformin-induced mTOR inhibition in an AMPK-dependent manner. ( a ) Metformin decreased the expression of phosphorylated mTOR, as well as its effectors p70S6K and 4EBP1. ( b and c ) Specific AMPK inhibitor compound C ( b ) and AMPK siRNA ( c ) abrogated metformin-induced lymphoma cell growth inhibition and cell cycle arrest. Comparing with the negative control (Con siRNA), Jurkat cells transfected with AMPK- α siRNA (AMPK siRNA) failed to induce phosphorylated ACC and inhibit phosphorylated mTOR. * P <0.001 comparing with the metformin group. + P <0.001 comparing with the Con siRNA group. ( d ) The expression of phosphorylated AKT remained unchanged during metformin treatment in Jurkat cells. ( e ) Cell sensitivity to metformin was not affected in Jurkat cells transfected with AKT

Article Snippet: The AMPK inhibitor compound C and the autophagy inhibitor 3-methyladenine were from Merck KGaA (Darmstadt, Germany).

Techniques: Inhibition, Expressing, Negative Control, Transfection

Journal: Cell Death & Disease

Article Title: Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy

doi: 10.1038/cddis.2012.13

Figure Lengend Snippet: The effect of metformin in murine lymphoma xenograft models. ( a ) In both B- and T-cell lymphoma models, intraperitoneal treatment of metformin, both at the high-dose (IP MET H) and low-dose (IP MET L) group, significantly diminished xenograft tumor size. ( b ) As compared with the control group (Con), decreased proliferative index Ki-67 was identified, while TUNEL staining was negative in the metformin group (MET). Immunohistochemical study showed increased numbers of cells positive for phosphorylated AMPK, but decreased cells positive for phosphorylated mTOR in the metformin-treated tumors

Article Snippet: The AMPK inhibitor compound C and the autophagy inhibitor 3-methyladenine were from Merck KGaA (Darmstadt, Germany).

Techniques: Control, TUNEL Assay, Staining, Immunohistochemical staining

Journal: Cell Death & Disease

Article Title: Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy

doi: 10.1038/cddis.2012.13

Figure Lengend Snippet: Metformin enhanced lymphoma cell sensitivity to the chemotherapeutic agent and stimulate autophagy. ( a ) In Daudi and Jurkat cells, metformin increased the cytotoxicity of the chemotherapeutic agent doxorubicin. ( b ) Metformin combined with doxorubicin induced less lymphoma cell growth inhibition in the AMPK siRNA group than in the Con siRNA group, * P <0.001 comparing with the Con siRNA group. ( c ) Autophagy-related LC3-II expression was significantly elevated in cells co-treated with metformin and doxorubicin. ( d ) Autophagy inhibitor 3-methyladenine abrogated lymphoma cell growth inhibition induced by co-treatment. ( e ) Combined oral metformin with doxorubicin significantly inhibited xenograft lymphoma growth, comparing with the control group or each agent alone. ( f ) The metformin/doxorubicin combination frequently induced lymphoma cell autophagy

Article Snippet: The AMPK inhibitor compound C and the autophagy inhibitor 3-methyladenine were from Merck KGaA (Darmstadt, Germany).

Techniques: Inhibition, Expressing, Control

Journal: Cell Death & Disease

Article Title: Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy

doi: 10.1038/cddis.2012.13

Figure Lengend Snippet: Metformin potentiated the effect of mTOR inhibitor to induce lymphoma cell autophagy. ( a ) In Daudi and Jurkat cells, metformin enhanced the growth-inhibitory effect of the mTOR inhibitor temsirolimus. ( b ) Metformin combined with temsirolimus induced less lymphoma cell growth inhibition in the AMPK siRNA group than in the Con siRNA group, * P <0.001 comparing with the Con siRNA group. ( c ) Co-treatment resulted in LC3-II upregulation. ( d ) Lymphoma cell growth inhibition was overcome by autophagy inhibitor 3-methyladenine. ( e ) Combined oral metformin with temsirolimus significantly inhibited xenograft lymphoma growth, comparing with the control group or each agent alone. ( f ) The metformin/temsirolimus combination frequently induced lymphoma cell autophagy

Article Snippet: The AMPK inhibitor compound C and the autophagy inhibitor 3-methyladenine were from Merck KGaA (Darmstadt, Germany).

Techniques: Inhibition, Control