Next Article in Journal
Waste Soybean Oil and Corn Steep Liquor as Economic Substrates for Bioemulsifier and Biodiesel Production by Candida lipolytica UCP 0998
Next Article in Special Issue
Elevated Expression of Calpain-4 Predicts Poor Prognosis in Patients with Gastric Cancer after Gastrectomy
Previous Article in Journal
PlGF and VEGF-A Regulate Growth of High-Risk MYCN-Single Copy Neuroblastoma Xenografts via Different Mechanisms
Previous Article in Special Issue
Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(10), 1614;

APEH Inhibition Affects Osteosarcoma Cell Viability via Downregulation of the Proteasome

Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy
Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy
Authors to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 11 July 2016 / Revised: 8 September 2016 / Accepted: 19 September 2016 / Published: 23 September 2016
(This article belongs to the Collection Advances in Molecular Oncology)
Full-Text   |   PDF [3545 KB, uploaded 23 September 2016]   |  


The proteasome is a multienzymatic complex that controls the half-life of the majority of intracellular proteins, including those involved in apoptosis and cell-cycle progression. Recently, proteasome inhibition has been shown to be an effective anticancer strategy, although its downregulation is often accompanied by severe undesired side effects. We previously reported that the inhibition of acylpeptide hydrolase (APEH) by the peptide SsCEI 4 can significantly affect the proteasome activity in A375 melanoma or Caco-2 adenocarcinoma cell lines, thus shedding new light on therapeutic strategies based on downstream regulation of proteasome functions. In this work, we investigated the functional correlation between APEH and proteasome in a panel of cancer cell lines, and evaluated the cell proliferation upon SsCEI 4-treatments. Results revealed that SsCEI 4 triggered a proliferative arrest specifically in osteosarcoma U2OS cells via downregulation of the APEH–proteasome system, with the accumulation of the typical hallmarks of proteasome: NF-κB, p21Waf1, and polyubiquitinylated proteins. We found that the SsCEI 4 anti-proliferative effect involved a senescence-like growth arrest without noticeable cytotoxicity. These findings represent an important step toward understanding the mechanism(s) underlying the APEH-mediated downregulation of proteasome in order to design new molecules able to efficiently regulate the proteasome system for alternative therapeutic strategies. View Full-Text
Keywords: acylpeptide hydrolase (APEH); proteasome; osteosarcoma cell lines; peptide inhibitor; anti-tumoral target acylpeptide hydrolase (APEH); proteasome; osteosarcoma cell lines; peptide inhibitor; anti-tumoral target

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Palumbo, R.; Gogliettino, M.; Cocca, E.; Iannitti, R.; Sandomenico, A.; Ruvo, M.; Balestrieri, M.; Rossi, M.; Palmieri, G. APEH Inhibition Affects Osteosarcoma Cell Viability via Downregulation of the Proteasome. Int. J. Mol. Sci. 2016, 17, 1614.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top