PI3K/mTOR and Bcl-2/Bcl-xL inhibition in leukemia 1 Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism
نویسندگان
چکیده
Correspondence: Dr. Steven Grant, Division of Hematology/Oncology, MCV Station Box 230, Virginia Commonwealth University, Richmond, VA 23298, Phone: 804-828-5211, Fax: 804828-8079, Email: [email protected], or Dr. Mohamed Rahmani, Virginia Commonwealth University, Massey Cancer Center, 401 college street, P.O. Box 980035, Richmond VA 23298. Phone: 804-628-1976, Fax: 804-225-3788, E-mail: [email protected]
منابع مشابه
Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism.
Effects of concomitant inhibition of the PI3K/AKT/mTOR pathway and Bcl-2/Bcl-xL (BCL2L1) were examined in human myeloid leukemia cells. Tetracycline-inducible Bcl-2 and Bcl-xL dual knockdown sharply increased PI3K/AKT/mTOR inhibitor lethality. Conversely, inducible knockdown or dominant-negative AKT increased, whereas constitutively active AKT reduced lethality of the Bcl-2/Bcl-xL inhibitor ABT...
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We previously showed that Bcl-xL and Mcl-1 cooperatively protect platinum-resistant ovarian cancer cells from apoptosis. Here we assessed the anticancer potential of combining ABT-737-induced inhibition of Bcl-xL with Mcl-1 inhibition via PI3K/Akt/mTOR pathway disruption using NVP-BEZ235. NVP-BEZ235 inhibited cell proliferation without inducing apoptosis. It strongly repressed Mcl-1 expression ...
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Background and aim: Cytokines are a large family of protein messengers. These proteins induce various cellular responses. Janus kinases (JAKs) are mediators of cytokine, activated JAKs phosphorylate signal transducers, and activators of transcription (STAT) proteins that regulate cell differentiation, proliferation, and apoptosis. Aberrant JAK/STAT signaling is involved in the oncogenesis of se...
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The B-cell lymphoma-2 (Bcl-2) family of pro-and anti-apoptotic proteins controls the mitochondrial pathway of apoptosis. Their central role in mediating the final common pathway of apoptosis in response to internal and external stressors makes them attractive therapeutic targets in neoplastic cells, which are often " primed " for apoptosis. The major anti-apoptotic proteins are Bcl-2, Bcl-xL an...
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