Pimozide also exerts chemotherapy and radiotherapy-sensitizing effects in cancer cells and acts as an inhibitor of STAT-3 and STAT-5 signaling proteins with potential activity in leukemia, liver and prostate cancer.
This review focuses on the role of STAT3 in pathogenesis i.e., proliferation, differentiation, migration, and apoptosis of hematological malignancies viz. leukemia, lymphoma and myeloma, and briefly highlights the potential therapeutic approaches developed against STAT3 activation pathway.
In this review, the roles of STAT3 in the pathogenesis, diagnosis, treatment and prognosis of leukemia are discussed in the aspects of cell proliferation, differentiation and apoptosis, with the aim to further clarify the roles of STAT3 in leukemia, and shed light into possible novel targets and strategies for clinical diagnosis and treatment.
The antitumor efficacy of this strategy is further enhanced in immunocompetent mice by combining direct leukemia-specific cytotoxicity with immunogenic effects of STAT3 blocking/TLR9 triggering.
Here we investigated the STAT3/myeloid cell leukemia 1 (MCL1) signaling pathway as a target to overcome the resistance of glioma cells to the Bcl-2-inhibiting synthetic BH3 mimetic ABT-737.
Downregulation of STAT3 phosphorylation enhances tumoricidal effect of IL-15-activated dendritic cell against doxorubicin-resistant lymphoma and leukemia via TNF-α.
In the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, STAT3 is one of the most prominent prognosis factors for cancer and leukemia.
Genotype analyses showed that two SNPs, namely rs17886724 and rs2293157 located in STAT3 and STAT5, respectively, were significantly associated with leukemia (p < 0.05 for all).
Hyperphosphorylation at the Y705 residue of signal transducer and activator of transcription 3 (STAT3) is implicated in tumorigenesis of leukemia and some solid tumors.
Our data indicate that resveratrol contributes to inhibiting growth, inducing apoptosis and cell cycle arrest in the three leukemia cell lines (Jurkat, SUP-B15, and Kasumi-1), and reducing the phosphorylation of STAT3, meanwhile modulating the expression of Bcl-2 and Bax.
Our results indicated that (1) the expression of TEL-FGFR3 but not DeltaHLH-TEL-FGFR3 resulted in efficient focus formation in NIH/3T3 cells and conferred interleukin 3 independence to Ba/F3 cells by a constitutive tyrosine kinase activity probably through oligomerization by the HLH domain of TEL; (2) although effector proteins including classical mitogen-activated protein kinase (MAPK), p38 MAPK, phosphatidylinositol 3-kinase (PI3-K), mammalian target or rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT-3) and STAT-5 were activated in TEL-FGFR3 transformants, the growth of the transformants was inhibited by SU5402 (concentration that inhibits 50% [IC5)]=5 microM) and the PI3-K inhibitor, LY294002 (IC5)=10 microM) and wortmannin (IC50=5 microM), but not by U0126, SB203580, or rapamycin; and (3) injection of TEL-FGFR3 transformants induced lethal leukemia into syngeneic mice.