Bioengineered arginase I increases caspase-3 expression of hepatocellular and pancreatic carcinoma cells despite induction of argininosuccinate synthetase-1.

Autor: Glazer ES; Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA., Kaluarachchi WD, Massey KL, Zhu C, Curley SA
Jazyk: angličtina
Zdroj: Surgery [Surgery] 2010 Aug; Vol. 148 (2), pp. 310-8. Date of Electronic Publication: 2010 May 13.
DOI: 10.1016/j.surg.2010.03.022
Abstrakt: Background: Hepatocellular and pancreatic carcinomas are often auxotrophic for L-arginine, a semi-essential amino acid. The purpose of this study was to investigate cancer cell death using a significantly more active, cobalt-substituted bioengineered arginase.
Methods: Panc-1, a human pancreatic carcinoma cell line, and Hep 3B, a human hepatocellular carcinoma cell line, were exposed to L-arginase. Flow cytometry was used to measure expression of Ki-67, caspase-3, and argininosuccinate synthetase-1 (ASS-1) 4 days after treatment. An MTT assay measured proliferation. The Student t test determined statistical significance.
Results: Viability decreased by 31% +/- 2% for Panc-1 cells (P < .0001) and 34% +/- 1% (P < .0001) for Hep 3B cells after treatment. Both cell lines demonstrated a 4-fold increase activated caspase-3 expression after high dose treatment (P < .01), and 5-fold increase in ASS-1 expression (P < .002). Ki-67 expression did not vary in Hep 3B cells but decreased for Panc-1 cells (P < .015). The 50% inhibitory concentration was 8-fold higher for Panc-1 cells than for Hep 3B cells (P < .03).
Conclusion: Increased ASS-1 expression by these cells, in order to increase L-arginine concentration, is inadequate, suggesting a mechanism by which arginine depletion can be used in multimodality therapy for arginine-dependent cancers.
(Copyright 2010 Mosby, Inc. All rights reserved.)
Databáze: MEDLINE
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