Aurora-B and HDAC synergistically regulate survival and proliferation of lymphoma cell via AKT, mTOR and Notch pathways

Wang, Chong; Chen, Jing; Cao, Wenhui; Sun, Ling; Sun, Hui; Liu, Yanfang

doi:10.1016/j.ejphar.2015.11.049

Cited by 40 publications

(33 citation statements)

References 38 publications

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“…However, Guise AJ et al identified that AURKB induced cell cycle progression through regulating its substrate Class IIa HDACs [87]. In consistence with Guise AJ group, it has been shown that AURKB and HDACs synergistically regulate cell survival and proliferation in lymphoma via activating AKT/mTOR signaling pathway [88]. …”

Section: The Roles Of Aurora Kinases In Cancermentioning

confidence: 99%

“…Inhibition of AURKB decreases the expression of Cyclin B1 and Cyclin D1, and elevates the Caspase 3 expression in lymphoma cells [88]. All of these data indicate that aberrant expression of AURKB might induce the cell survival-associated proteins expression and decrease the expression of pro-apoptosis proteins, although the precise molecular mechanism remains elusive.…”

Section: The Roles Of Aurora Kinases In Cancermentioning

confidence: 99%

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Aurora kinases: novel therapy targets in cancers

et al. 2017

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Section: The Roles Of Aurora Kinases In Cancermentioning

confidence: 99%

Section: The Roles Of Aurora Kinases In Cancermentioning

confidence: 99%

Aurora kinases: novel therapy targets in cancers

et al. 2017

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“…It has been demonstrated that aurora B kinase, which exists in a complex with survivin and mTOR, synergistically regulates survival and proliferation of leukemia and lymphoma cells via crass-talk with AKT, mTOR and NOTCH signaling pathways (73,74). Moreover, several studies have reported that aurora kinase inhibitors induce cell-cycle arrest and apoptosis of cancer cells through p38 MAPK and AKT/mTOR signaling (75,76).…”

Section: Effect Of Melatonin On Barasertib-induced Cytotoxicity Apopmentioning

confidence: 99%

Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes but not Normal Lymphocytes

Zhelev

Ivanova

Bakalova

et al. 2017

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The present study demonstrates specific sensitization of leukemia lymphocytes towards anticancer drugs using melatonin and clarifies the role of reactive oxygen species (ROS) for induction of apoptosis. The study covers four conventional and 11 new-generation anticancer drugs. Four parameters were analyzed simultaneously in leukemia and normal lymphocytes treated with drug, melatonin, or their combination: cell viability, induction of apoptosis, level of reactive oxygen species (ROS), and level of protein-carbonyl products. Almost all investigated combinations of melatonin with new-generation anticancer drugs were characterized by synergistic cytotoxicity towards leukemia lymphocytes, while the combinations with conventional drugs exhibited additive or antagonistic effects on cell viability. In leukemia lymphocytes, the additive cytotoxicity of doxorubicin plus melatonin was accompanied by low levels of ROS and protein-carbonyl products, as well as by suppression of apoptosis. In normal lymphocytes, none of the studied parameters changed significantly compared to cells treated with doxorubicin only. The combinations of everolimus plus melatonin and barasertib plus melatonin exhibited impressive synergistic cytotoxic effects on leukemia lymphocytes but did not affect the viability of normal lymphocytes. In leukemia cells, the synergistic cytotoxicity was accompanied by strong induction of apoptosis but a decrease of ROS to a level below that of the control. In normal lymphocytes, these combinations did not affect the level of ROS nor of protein-carbonyl products, and did not induce apoptosis. The data suggest that melatonin is a promising supplementary component in chemotherapy which allows the therapeutic doses of anticancer drugs to be reduced, minimizing their side-effects.

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“…Resulting tumor cell non-diploidy contributes to uncontrolled cell cycle progression and promotes cell survival. These effects are synergistic with histone deacetylases in regulating cell proliferation and survival through activation of AKT/mTOR signaling in lymphomas [27]. AK C is overexpressed in several cancers and cancer cell lines, but its role in carcinogenesis and effect on tumor cell proliferation is unclear [28,29].…”

Section: Role Of Aurora Kinases In Tumorigenesismentioning

confidence: 99%

“…AK C is overexpressed in several cancers and cancer cell lines, but its role in carcinogenesis and effect on tumor cell proliferation is unclear [28,29]. Similar to AK B, overexpressed AK C binds to and localizes with the IAP protein survivin in mitotic cells [15,27]. However, a clear role for AK C in tumorigenesis has not been identified.…”

Section: Role Of Aurora Kinases In Tumorigenesismentioning

confidence: 99%

Novel Aurora Kinase Inhibitor-Based Combination Therapies for PTCL

Tenneti¹,

Davis²,

Mahadevan³

2019

Peripheral T-Cell Lymphomas

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Peripheral T-cell lymphomas (PTCLs) are a rare, heterogeneous group of T-cell non-Hodgkin's lymphomas (T-NHL) that display distinct clinical and biological features. Despite a detailed understanding of PTCL transformation, there is no current accepted standard of care for newly diagnosed or relapsed/refractory (r/r) patients. PTCL are highly proliferative neoplasms with an immunosuppressive microenvironment that elaborates drug resistance to current therapies with poor outcomes. Aurora kinases (AKs) are a family of mitotic oncogenic serine/threonine kinases (A, B/C) that are aberrantly expressed in PTCL, providing a growth advantage. Alisertib, an AK-A inhibitor, blocks the mitotic phase of the cell cycle resulting in apoptosis. Preclinical and clinical trials in PTCL demonstrated an ~30% response rate in r/r PTCL similar to other investigational agents. In order to improve response rates, alisertib-based combination therapies were tested with HDAC inhibitors, romidepsin and vorinostat, in phase Ib trials. To improve response rates to alisertib, we evaluated alisertib-induced polyploidy as a drug resistance mechanism by targeting microtubules with vincristine. In addition, we also targeted immunosuppression-induced proliferation with an anti-PD-L1 antibody and PI3K inhibition in PTCL. Targeting aberrant proliferation and immunosuppression is a novel strategy that warrants evaluation in clinical trials for PTCL, an unmet clinical need.

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Aurora-B and HDAC synergistically regulate survival and proliferation of lymphoma cell via AKT, mTOR and Notch pathways

Cited by 40 publications

References 38 publications

Aurora kinases: novel therapy targets in cancers

Aurora kinases: novel therapy targets in cancers

Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes but not Normal Lymphocytes

Novel Aurora Kinase Inhibitor-Based Combination Therapies for PTCL

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