CUDC-907 enhances TRAIL-induced apoptosis through upregulation of DR5 in breast cancer cells

Li, Zhaojun; Hou, Ya‐Jun; Hao, Gangping; Pan, Xiaoxuan; Fei, Hong-rong; Wang, Fengze

doi:10.1007/s12079-020-00558-3

Cited by 19 publications

(11 citation statements)

References 32 publications

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“…Our results demonstrated the effect of CUDC-907 in inhibiting the PI3K/AKT, HDACs, and enhancing the H3K9Ac levels in NB. Numerous reports in different cancers have shown similar results of the CUDC-907-mediated inhibition of PI3K, HDACs, and related proteins [ 20 , 21 , 32 , 35 , 37 , 38 ]. MYCN is one of the most important prognostic factors for the NB progression [ 46 ].…”

Section: Discussionmentioning

confidence: 65%

“…In glioblastoma, CUDC-907 induces G1 cell cycle arrest through CDKN1A promoter hyperacetylation-driven transcriptional activation and downregulation of CDK1 [ 36 ], while in lung fibroblast cells, CUDC-907 blocks G1 and S phase [ 37 ]. In breast cancer, CUDC-907 enhances TRAIL-induced apoptosis through the upregulation of cell survival proteins, including XIAP, Bcl-xL, and Bcl-2 [ 38 ]. The oncogenic activation of PI3K/AKT signaling pathway regulates multiple parallel signaling pathways, which are known to be involved in metabolism, proliferation, motility, and autophagy in different cancers [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

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Dual Targeting of PI3K and HDAC by CUDC-907 Inhibits Pediatric Neuroblastoma Growth

Chilamakuri

Agarwal

2022

Cancers

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The dysregulation of PI3K, HDACs, and MYCN are well known for promoting multiple cancer types, including neuroblastoma (NB). Targeting the upstream regulators of MYCN, including HDACs and PI3K, was shown to suppress cancer growth. In the present study, we analyze different NB patient datasets to reveal that high PI3K and HDAC expression is correlated with overall poor NB patient survival. High PI3K level is also found to be associated with high MYCN level and NB stage progression. We repurpose a dual inhibitor CUDC-907 as a single agent to directly target both PI3K and HDAC in NB. We use in vitro methodologies to determine the efficacy and selectivity of CUDC-907 using six NB and three control fibroblast cell lines. Our results show that CUDC-907 significantly inhibits NB proliferation and colony growth, induces apoptosis, blocks cell cycle progression, inhibits MYCN, and enhances H3K9Ac levels by inhibiting the PI3K/AKT signaling pathway and HDAC function. Furthermore, CUDC-907 significantly inhibits NB tumor growth in a 3D spheroid tumor model that recapitulates the in vivo tumor growth. Overall, our findings highlight that the dual inhibition of PI3K and HDAC by CUDC-907 is an effective therapeutic strategy for NB and other MYC-dependent cancers.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Dual Targeting of PI3K and HDAC by CUDC-907 Inhibits Pediatric Neuroblastoma Growth

Chilamakuri

Agarwal

2022

Cancers

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“…Some chemotherapy agents induce cell cycle arrest by upregulating the expression of inhibitors of cyclins and CDKs. [ 21,22 ] We found that treatment with SBT‐A upregulated the expression of p21 in both the HepG2 and Huh7 cells and increased that of p27 only in the HepG2 cells.…”

Section: Discussionmentioning

confidence: 92%

Scutebarbatine A induces cytotoxicity in hepatocellular carcinoma via activation of the MAPK and ER stress signaling pathways

Feng

et al. 2021

J Biochem & Molecular Tox

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Scutebarbatine A (SBT‐A), a diterpenoid alkaloid found in the root of Scutellaria barbata D. Don, has been reported to induce the apoptosis of A549 cells. In this study, we investigated the antitumor activity of SBT‐A in human hepatocellular carcinoma (HCC) cells and the potential underlying mechanisms. Our results showed that SBT‐A inhibited the growth of HCC cells in a dose‐dependent manner. SBT‐A treatment caused cell cycle arrest and decreased the expression of cyclin B1, cyclin D1, p‐Cdc2, and p‐Cdc25C. SBT‐A triggered cell apoptosis via a caspase‐dependent pathway, and cell viability was partially restored by pretreatment with the pan‐caspase inhibitor Z‐VAD‐FMK. In HCC cells, treatment with SBT‐A increased the phosphorylation of extracellular signal‐regulated kinase 1 and 2 (ERK1/2), c‐Jun N‐terminal kinase 1 and 2 (JNK1/2), and p38 mitogen‐activated protein kinase (p38 MAPK). Moreover, SBT‐A activated endoplasmic reticulum (ER) stress through the upregulation of protein kinase RNA‐like ER kinase (PERK), activating transcription factor 4 (ATF‐4), and CCAAT‐enhancer‐binding protein (C/EBP) homologous protein (CHOP). Our data indicate that SBT‐A inhibits the proliferation of HCC cells and triggers their apoptosis via the activation of MAPK and ER stress. SBT‐A is a potential agent for the treatment of HCC.

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“…Importantly, CUDC-907 enhanced the phosphorylation of p38 MAPK and JNK. JNK inhibition blocked CUDC-907-induced DR5 upregulation (30). Collectively, these findings suggested that CUDC-907 potentiated TRAIL-mediated apoptosis by lowering the levels of anti-apoptotic proteins and simultaneously stimulating the levels of DR5.…”

Section: Targeting Of Oncogenic Network In Trail Pathwaymentioning

confidence: 67%

“…CUDC-907 is an efficient dual-acting inhibitor of PI3K (phosphoinositide 3-kinase) and HDAC (histone deacetylase) (30). CUDC-907 stimulated DR5 expression, lowered the levels of anti-apoptotic proteins Bcl-2, Bcl-xL and XIAP.…”

Section: Targeting Of Oncogenic Network In Trail Pathwaymentioning

confidence: 99%

TRAIL mediated signaling in different cancers: cancer in the "Crosshairs"

Farooqi

Naureen

Yılmaz

et al. 2020

Cell Mol Biol (Noisy-le-grand)

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Cancer is a therapeutically challenging disease because of its heterogeneous and multifaceted nature. Decades of research have sequentially and systematically enabled us to develop a sharper and better understanding of the heterogeneous nature of cancer. Genetic, genomic and proteomic studies have unraveled wide-ranging signaling cascades which play cornerstone role in disease onset and progression. More importantly, activation of pro-survival signaling and loss of apoptosis also play critical role in cancer progression. TRAIL-mediated signaling pathway has emerged as one of the most comprehensively analyzed cascade because of its exceptional ability to target cancer cells while leaving normal cells intact. TRAIL discovery and landmark achievements related to TRAIL/TRAIL-receptor signaling pathway attracted the attention of researchers. Therefore, scientists started to add missing pieces to an incomplete jig-saw puzzle and allowed contemporary researchers to conceptualize a better molecular snapshot of TRAIL-induced signaling in various cancers. Circumstantial evidence illuminated a functionally unique "push and pull" between anti-apoptotic and pro-apoptotic proteins in different cancers. Overexpression of anti-apoptotic proteins and inactivation of pro-apoptotic proteins shifted the balance towards loss of apoptosis. There has been a breakneck increase in the number of clinical trials related to TRAIL-based therapeutics which validate the true pharmacological potential of TRAIL-based therapeutics as effective anticancer agents. However, apart from advancements in our clinical understanding about the efficacy of TRAIL-based therapeutics, researchers have also faced setbacks in the field of translational medicine. Therefore, in this review, we have attempted to set spotlight on the most recent and landmark discoveries which have leveraged our understanding related to TRAIL-mediated signaling altogether to a new level.

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CUDC-907 enhances TRAIL-induced apoptosis through upregulation of DR5 in breast cancer cells

Cited by 19 publications

References 32 publications

Dual Targeting of PI3K and HDAC by CUDC-907 Inhibits Pediatric Neuroblastoma Growth

Dual Targeting of PI3K and HDAC by CUDC-907 Inhibits Pediatric Neuroblastoma Growth

Scutebarbatine A induces cytotoxicity in hepatocellular carcinoma via activation of the MAPK and ER stress signaling pathways

TRAIL mediated signaling in different cancers: cancer in the "Crosshairs"

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