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Cancer Lett. 2002 Dec 10;187(1-2):163-8.

Anti-tumor promoting effects of palmitoyl: protein thioesterase inhibitors against a human neurotumor cell line.

Author information

1
Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA. dawg@midway.uchicago.edu

Abstract

Inhibiting the depalmitoylation of proteins disrupts cell survival signaling in tumor cells and leads to increased cell death. We chemically synthesized a non-hydrolyzable analog of the palmitoyl-cysteine thioester linkage (AcG-alpha-ketoamido-palmitoyl diamino propionate-VKIKK) (DAPKA) and showed that it inhibits palmitoyl:protein thioesterase (PPT1) in an in vitro assay using a specific fluorescent-based (4-methylumbelliferyl-beta-gluco-6-thiopalmitate) assay. We then showed that it killed cultured tumor cells and enhanced the killing of neurotumor cells by chemotherapeutic drugs such as etoposide and adriamycin. Overexpression of PPT1 protected against apoptosis induced by etoposide and the ketoamide and the inhibitory effect of the two was additive.

PMID:
12359364
DOI:
10.1016/s0304-3835(02)00403-2
[Indexed for MEDLINE]

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