Proteasome inhibitor carfilzomib interacts synergistically with histone deacetylase inhibitor vorinostat in Jurkat T-leukemia cells

Gao, Minjie; Yi, Tao; Hou, Jun; Yang, Guang; Wu, Xiaosong; Xu, Hui; Tompkins, Van S.; Han, Ying; Wu, Huiqun; Zhan, Fenghuang; Shi, Jumei

doi:10.1093/abbs/gmu030

Cited by 12 publications

(8 citation statements)

References 23 publications

(29 reference statements)

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“…Vorinostat, a pan-HDAC inhibitor, is used for the treatment of cutaneous T-cell lymphoma. A recent study showed that the proteasome inhibitor carfilzomib interacts synergistically with vorinostat in jurkat T-leukemia cells 50 . Two previous studies also found the synergy between proteasome inhibitors and imatinib mesylate in chronic myeloid leukemia 51 52 .…”

Section: Resultsmentioning

confidence: 99%

Regulation rewiring analysis reveals mutual regulation between STAT1 and miR-155-5p in tumor immunosurveillance in seven major cancers

Chen

Jiang

Mitra

et al. 2015

Sci Rep

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Transcription factors (TFs) and microRNAs (miRNAs) form a gene regulatory network (GRN) at the transcriptional and post-transcriptional level in living cells. However, this network has not been well characterized, especially in regards to the mutual regulations between TFs and miRNAs in cancers. In this study, we collected those regulations inferred by ChIP-Seq or CLIP-Seq to construct the GRN formed by TFs, miRNAs, and target genes. To increase the reliability of the proposed network and examine the regulation activity of TFs and miRNAs, we further incorporated the mRNA and miRNA expression profiles in seven cancer types using The Cancer Genome Atlas data. We observed that regulation rewiring was prevalent during tumorigenesis and found that the rewired regulatory feedback loops formed by TFs and miRNAs were highly associated with cancer. Interestingly, we identified one regulatory feedback loop between STAT1 and miR-155-5p that is consistently activated in all seven cancer types with its function to regulate tumor-related biological processes. Our results provide insights on the losing equilibrium of the regulatory feedback loop between STAT1 and miR-155-5p influencing tumorigenesis.

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Section: Resultsmentioning

confidence: 99%

Regulation rewiring analysis reveals mutual regulation between STAT1 and miR-155-5p in tumor immunosurveillance in seven major cancers

Chen

Jiang

Mitra

et al. 2015

Sci Rep

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“…Previous studies in various tumor cells have indicated that bortezomib or HDACi-induced lethality is related to ROS generation [ 17 – 20 ]. Moreover, lethal effects induced by the combined treatment with proteasome inhibitor and HDACi in leukemia and lymphoma cells have also been demonstrated to proceed through a ROS-dependent mechanism [ 21 , 22 ]. In the present study, we showed that combined treatment with carfilzomib and LBH589 induced a marked increase in ROS in MM cells and the free radical scavenger NAC attenuated the oxidative stress, as well as the subsequent apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Activity of Carfilzomib and Panobinostat in Multiple Myeloma Cells via Modulation of ROS Generation and ERK1/2

Gao

Yang

et al. 2015

BioMed Research International

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Relapse of disease and subsequent resistance to established therapies remain as major challenges in the treatment of multiple myeloma (MM). New therapeutic options are needed for these extensively pretreated patients. To explore an optimized combinational therapy, interactions between the irreversible proteasome inhibitor carfilzomib exhibiting a well-tolerated side-effect profile and histone deacetylase inhibitor (HDACi) panobinostat (LBH589) were examined in MM cells. Coadministration of carfilzomib and LBH589 led to a synergistic inhibition of proliferation in MM cells. Further studies showed that the combined treatment synergistically increased mitochondrial injury, caspase activation, and apoptosis in MM cells. Lethality of the carfilzomib/LBH589 combination was associated with the reactive oxygen species (ROS) generation and ERK1/2 inactivation. In addition, the free radical scavenger N-acetylcysteine (NAC) could block carfilzomib and LBH589-induced oxidative stress and the subsequent apoptosis. Together, these findings argue that the strategy of combining carfilzomib and LBH589 warrants attention in MM.

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“…Romidepsin is one of a depsipeptide small molecule (MW=540.7) belonging to histone deacetylase (HDAC) inhibitors (Valdez et al, 2015). Several HDAC inhibitors have been reported to act as tumor suppressors that either indirectly contribute to tumor cell death by inducing changes in cell cycle distribution or directly induce apoptosis in various cancer cells (Vinodhkumar et al, 2008;Gao et al, 2014). Interestingly, HDAC inhibitors are known to induce expression of multiple T cell chemokines such as C-C motif chemokine ligand 5 (CCL5) and C-X-C motif chemokine ligand 10 (CXCL10), thus recruiting effectors T-cells to tumor cells.…”

Section: Original Articlementioning

confidence: 99%

Improving Combination Cancer Therapy by Acetaminophen and Romidepsin in Non-small Cell Lung Cancer Cells

Lee

Park

Kim

2019

BSL

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Combination chemotherapy is more effective than mono-chemotherapy and is widely used in clinical practice for enhanced cancer treatment. In this study, we investigated the potential synergistic effects of acetaminophen, a common component in many cold medicines, and romidepsin, a histone deacetylase (HDAC) inhibitor, in the A549 non-small cell lung cancer (NSCLC) cell line. The combination of acetaminophen and romidepsin also exerted significant cytotoxicity and apoptosis induced by activation of caspase-3 on tumor cells in vitro. Moreover, combination therapy significantly induced increased production of chemokines that stimulate migration of activated T-cells into tumor cells. This mechanism can lead to active T-cell mediated anti-tumor immunity in addition to the direct cytotoxic chemotherapeutic effect. Activated T-cells led to enhanced cytotoxicity in drug-treated A549 cells through interaction with tumor cells. These results suggested that the interaction between the two drugs is synergistic and significant. In conclusion, our data showed that the use of romidepsin and low concentrations acetaminophen could induce effective anti-tumor effects via enhanced tumor immune and direct cytotoxic chemotherapeutic responses. The combination of acetaminophen with romidepsin should be considered as a promising strategy for the treatment of lung cancer.

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Proteasome inhibitor carfilzomib interacts synergistically with histone deacetylase inhibitor vorinostat in Jurkat T-leukemia cells

Cited by 12 publications

References 23 publications

Regulation rewiring analysis reveals mutual regulation between STAT1 and miR-155-5p in tumor immunosurveillance in seven major cancers

Regulation rewiring analysis reveals mutual regulation between STAT1 and miR-155-5p in tumor immunosurveillance in seven major cancers

Synergistic Activity of Carfilzomib and Panobinostat in Multiple Myeloma Cells via Modulation of ROS Generation and ERK1/2

Improving Combination Cancer Therapy by Acetaminophen and Romidepsin in Non-small Cell Lung Cancer Cells

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