The Aurora kinase inhibitor VE-465 has anticancer effects in pre-clinical studies of human hepatocellular carcinoma

Lin, Zhong; Hsu, Hey Chi; Hsu, Chih Hung; Yeh, Pei Yen; Huang, Chi Ying F.; Huang, Yung Feng; Chen, Te Jung; Kuo, Sung‐Hsin; Hsu, Chiun; Hu, Fang; Jeng, Yung‐Ming; Chung, Ying Chien; Cheng, Ann‐Lii

doi:10.1016/j.jhep.2008.10.022

Cited by 43 publications

(39 citation statements)

References 34 publications

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“…Several reports have shown that pharmacologic inhibition of Aurora A leads to apoptosis and our results suggest that this may due in part to mitotic stabilization of Bim. 34,50,51 Interestingly, Li et al conclusively demonstrated that apoptosis induced by Aurora A inhibition occurs through the intrinsic mitochondrial pathway requiring the activity of either Bax or Bak. 34 This is consistent with the activation of a BH3-only protein such as Bim, which functions in part by activating pro-apoptotic Bcl-2 family members Bax and Bak.…”

Section: Discussionmentioning

confidence: 99%

BimEL is phosphorylated at mitosis by Aurora A and targeted for degradation by βTrCP1

et al. 2013

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Section: Discussionmentioning

confidence: 99%

BimEL is phosphorylated at mitosis by Aurora A and targeted for degradation by βTrCP1

et al. 2013

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“…VE-465 treatment causes cell death in myeloma cell lines, primary myeloma plasma cells, and hepatocellular carcinoma cells [14,15]. Combined with dexamethasone, VE-465 has improved cytotoxic effects compared with the use of either agent alone, even in cells that are resistant to the single agents in myeloma cells [14].…”

Section: Introductionmentioning

confidence: 99%

“…Combined with dexamethasone, VE-465 has improved cytotoxic effects compared with the use of either agent alone, even in cells that are resistant to the single agents in myeloma cells [14]. In vivo, VE-465 suppresses Aurora kinase activity, prevents tumor growth, and induces apoptosis in a Huh-7 xenograft model [15]. …”

Section: Introductionmentioning

confidence: 99%

The Aurora Kinases Inhibitor VE-465 is a Novel Treatment for Glioblastoma Multiforme

et al. 2013

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Glioblastoma multiforme (GBM) is one of the most common and aggressive types of primary brain tumor. After complete surgical resection combined with radiation and chemotherapy, approximately 10% of patients survive for more than 5 years. Therefore, a novel therapy for GBM is needed. Aurora-A (AURKA) plays important roles in cell cycle regulation, such as centrosome maturation, chromatic separation, bipolar spindle assembly, and mitotic entry. To investigate the effects of AURKA inhibition, three GBM cell lines, including GBM 8401, GBM 8901, and U87-MG cells, were treated with the AURKA inhibitor VE-465. Sensitivities to VE-465, as indicated by 50% inhibitory concentration values for GBM 8401, GBM 8901, and U87-MG cells, were 6, 25, and 19 nM, respectively. Additionally, colony formation of GBM 8401 and GBM 8901 cells was decreased after treatment with the VE-465. VE-465 treatment increased polyploidy and p53 protein expression, and inhibited cell growth in a caspase-independent manner. Taken together, these results suggest that the inhibition of AURKA by a small-molecule inhibitor may have potential to serve as a novel therapeutic approach for GBM.

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“…They are found to be overexpressed in a variety of human cancers (9). Preclinical and clinical studies have shown promising therapeutic potential of Aurora kinase inhibitors in various cancers (10,11).…”

Section: Introductionmentioning

confidence: 99%

Nuclear Overexpression of Mitotic Regulatory Proteins in Biliary Tract Cancer: Correlation with Clinicopathologic Features and Patient Survival

Shen

Jeng³

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Mitosis dysregulation is common in cancers. This study explored the nuclear expression patterns and prognostic significance of mitotic regulatory proteins, including Aurora kinases, survivin, and p53, in biliary tract cancer (BTC). Archival tumor samples from 161 BTC patients who underwent surgery were tested for the expression of Aurora-A, Aurora-B, survivin, and p53 by immunohistochemistry. The potential endogeneity among the clinicopathologic variables and survival outcome was assessed by a generalized simultaneous equations model. Nuclear overexpression of Aurora-A, Aurora-B, survivin, and p53 was found in 79 (49.1%), 45 (28.0%), 55 (34.2%), and 55 (34.2%) patients, respectively. Intrahepatic cholangiocarcinoma, compared with the other two subtypes, had significantly higher proportions of nuclear overexpression of Aurora-B and survivin (37.8% and 47.3%, respectively). Simultaneous overexpression of Aurora-A and Aurora-B was correlated with that of p53. Overexpression of Aurora-B was also correlated with that of survivin and tumor grade. Our data indicate that simultaneous overexpression of Aurora-A and Aurora-B, suggesting dysregulated mitosis is associated with worse survival in patients with BTC. Independent prognostic factors for poor overall survival included simultaneous overexpression of Aurora-A and Aurora-B (hazard ratio, 1.997; 95% confidence interval, 1.239-3.219; P = 0.0045) and tumor grade (hazard ratio, 2.117; 95% confidence interval, 1.339-3.348; P = 0.0013) assessed by a multivariate analysis stratified by American Joint Committee on Cancer stage and p53 overexpression. Endogeneity testing suggested that nuclear overexpression of p53 and tumor type may influence patient survival through their interactions with Aurora-A/Aurora-B expression and tumor grade. (Cancer Epidemiol Biomarkers Prev 2009;18(2):417 -23)

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The Aurora kinase inhibitor VE-465 has anticancer effects in pre-clinical studies of human hepatocellular carcinoma

Cited by 43 publications

References 34 publications

BimEL is phosphorylated at mitosis by Aurora A and targeted for degradation by βTrCP1

BimEL is phosphorylated at mitosis by Aurora A and targeted for degradation by βTrCP1

The Aurora Kinases Inhibitor VE-465 is a Novel Treatment for Glioblastoma Multiforme

Nuclear Overexpression of Mitotic Regulatory Proteins in Biliary Tract Cancer: Correlation with Clinicopathologic Features and Patient Survival

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