The proteasome inhibitor bortezomib interacts synergistically with the histone deacetylase inhibitor suberoylanilide hydroxamic acid to induce T-leukemia/lymphoma cells apoptosis

Ql, Zhang; Wang, L; Yw, Zhang; Xx, Jiang; Yang, Fan; Wl, Wu; Janin, Anne; Chen, Zhiao; Zx, Shen; Sj, Chen; Wl, Zhao

doi:10.1038/leu.2009.41

Cited by 80 publications

(68 citation statements)

References 34 publications

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“…68,94 Interaction between inhibitors of the proteasome and HDAC inhibitors have been investigated, showing synergistic effect, in different types of cancer and future clinical applications of this combination should be considered. [95][96][97][98][99] Synergistic effects were shown for BZ in combination with tubacin and SAHA that inhibits HDAC6 resulting in a marked accumulation of ubiquitinated proteins. 100,101 Moreover, recent studies showed that disruption of autophagy, resulted in accumulation of ubiquitinated proteins and HDACs inhibitors, like Vorinostat, potentiates aggregates formation, super oxide generation and apoptosis.…”

Section: Histone Deacetylase Inhibitorsmentioning

confidence: 99%

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Role of ATF4 in regulation of autophagy and resistance to drugs and hypoxia

Rzymski¹,

Milani²,

Singleton³

et al. 2009

Cell Cycle

168

129

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Section: Histone Deacetylase Inhibitorsmentioning

confidence: 99%

“…100,101 Moreover, recent studies showed that disruption of autophagy, resulted in accumulation of ubiquitinated proteins and HDACs inhibitors, like Vorinostat, potentiates aggregates formation, super oxide generation and apoptosis. 96,98,102,103 …”

Section: Histone Deacetylase Inhibitorsmentioning

confidence: 99%

Role of ATF4 in regulation of autophagy and resistance to drugs and hypoxia

Rzymski¹,

Milani²,

Singleton³

et al. 2009

Cell Cycle

168

129

View full text Add to dashboard Cite

“…111 Recently, Bortezomib was reported to exhibit synergistic anti-tumor effects with histone deacetylase inhibitor for ATL cells in vitro and in vivo. 112 To evaluate the clinical efficacy of bortezomib in patients with ATL, large-scale phase II trials of bortezomib with or without other chemotherapeutic agents are urgently required.…”

Section: ) Proteasome Inhibitorsmentioning

confidence: 99%

Treatment of Adult T-cell Leukemia

Uozumi

2010

J Clin Exp Hematopathol

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Adult T-cell Leukemia (ATL) is an aggressive malignant disease of CD4 + T-cells associated with human T-cell leukemia virus type I (HTLV-I). Prognosis of ATL patients is directly correlated to the subtype of ATL. Treatment of the aggressive forms (acute and lymphoma types) of ATL remains inadequate, as most ATL patients receive conventional chemotherapy without stem cell rescue. At present, LSG15 is the standard chemotherapy for the treatment of aggressive ATL, but the efficacy of LSG15 in most patients is transient. To prolong median survival time, additional therapies for maintenance of complete response (CR) are needed after achieving CR by induction chemotherapy. Improved outcome after allogeneic stem cell transplantation (allo-SCT), despite a high incidence of graft-versus-host disease, has been reported. Thus, allogeneic bone marrow transplantation and allogeneic peripheral blood SCT may have great potential for eradication of HTLV-1 and cure of ATL. Recently, reduced-intensity conditioning stem cell transplantation was also reported to be effective for ATL. Although several issues, including selection criteria for patients and sources of stem cells remain to be resolved, allo-SCT may be considered as a treatment option for patients with aggressive ATL. To evaluate whether allo-SCT is more effective than the standard chemotherapy (LSG15) for aggressive ATL, an upfront phase II clinical trial of JCOG-LSG is now being planned. Novel innovative targeted strategies, such as antiretroviral therapy, arsenic trioxide, nuclear factor-kB inhibitors, proteasome inhibitors, histone deacetylase inhibitors, several monoclonal antibodies including anti-CC chemokine receptor 4, anti-folate, purine nucleotide phosphorylase inhibitor, mTOR (mammalian target of rapamycin) inhibitor, bendamustine, small molecule Bcl-2 inhibitors and Tax-targeted immunotherapy, should be promptly studied in order to develop curative treatments for ATL in the near future. 〔J Clin Exp Hematopathol 50(1) : 9-25, 2010〕

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“…Previous studies have shown that the synchronous inhibition of the proteasome and Hdac functions against many non-solid tumors, including multiple myelomas, mantle cell lymphoma and T-cell lymphoma (7)(8)(9). However, the possible effects and therapeutic mechanisms of this combination in Hela cells remain to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Synergistic induction of apoptosis in HeLa cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitor SAHA

Jiang

Wang²,

Su³

et al. 2010

Mol Med Rep

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Abstract. Proteasome inhibitors and histone deacetylase (Hdac) inhibitors are two promising groups of anti-cancer agents. in this study, we examined the apoptotic effects of the proteasome inhibitor bortezomib and Hdac inhibitor suberoylanilide hydroxamic acid (SaHa) in human cervical carcinoma Hela cells. compared to treatment with bortezomib or SaHa alone, co-exposure with these two agents synergistically resulted in the massive apoptosis of Hela cells, consistent with a significant increase in caspase-3 activation. We then investigated the mechanisms underlying this effect. The combination of bortezomib and SaHa caused an increase in the ratio of bax/bcl-2 expression, inhibited the nuclear transportation of nF-κB, and down-regulated akt expression and phosphorylation in Hela cells. in conclusion, bortezomib and SaHa cooperatively stimulate apoptosis in Hela cells through the inhibition of several cyto-protective signalling pathways. This is the first report of synergistic apoptotic effect achieved with a proteasome inhibitor and Hdac inhibitor in Hela cells. Thus, the results build the framework for clinical trials using combined proteasome and Hdac inhibition in the treatment of human cervical carcinoma. IntroductionHuman cervical carcinoma is one of the most common malignancies in women. although conventional chemotherapy induces a high rate of complete remission, relapse is frequently observed and these patients have a poor clinical outcome (1).insights into the pathogenesis of human cervical carcinoma reveal alterations in cell proliferation and apoptosis, and the dysregulation of multiple intracellular signaling pathways, such as nuclear factor nF-κB and akt (2). Therefore, improved approaches to treating cervical carcinoma are likely to result from the investigation of those non-chemotherapeutic agents that specifically target the pathways that cancer cells depend on for their survival.Protein degradation by proteasomes is vital to cell viability, ensuring the exact regulation of the breakdown of the metabolic enzymes, transcription factors and proteins involved in the cell cycle and cell death. Proteasome inhibitors represent a new treatment strategy targeting the 26S proteasome, a component of the ubiquitin-proteasome complex responsible for the degradation of unwanted cellular proteins. These inhibitors show significant activity against various cancer cells, leading to the induction of cellular apoptosis (3). Bortezomib (Velcade, PS-341) is the first clinically available proteasome inhibitor, and its use was recently reported in the treatment of human cervical carcinoma (4).Mutation or aberrant expression of genes, especially those responsible for the cell cycle and apoptosis, is commonly related to the tumorigenesis of many types of cancer. The acetylation and deacetylation of histone play an important role in the regulation of these genes. Histone deacetylase (Hdac) inhibitors constitute a group of compounds that promote histone acetylation, chromatin uncoiling and the transcription of genes involv...

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The proteasome inhibitor bortezomib interacts synergistically with the histone deacetylase inhibitor suberoylanilide hydroxamic acid to induce T-leukemia/lymphoma cells apoptosis

Cited by 80 publications

References 34 publications

Role of ATF4 in regulation of autophagy and resistance to drugs and hypoxia

Role of ATF4 in regulation of autophagy and resistance to drugs and hypoxia

Treatment of Adult T-cell Leukemia

Synergistic induction of apoptosis in HeLa cells by the proteasome inhibitor bortezomib and histone deacetylase inhibitor SAHA

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