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

Evan Glazer, Warna D. Kaluarachchi, Katheryn L. Massey, Cihui Zhu, Steven A. Curley

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)310-318
Number of pages9
JournalSurgery
Volume148
Issue number2
DOIs
StatePublished - May 10 2010

Fingerprint

Argininosuccinate Synthase
Arginase
Caspase 3
Hepatocellular Carcinoma
Arginine
Cell Line
Essential Amino Acids
Therapeutics
Cobalt
Pancreatic Carcinoma
Inhibitory Concentration 50
Neoplasms
Flow Cytometry
Cell Death
Students

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Bioengineered arginase i increases caspase-3 expression of hepatocellular and pancreatic carcinoma cells despite induction of argininosuccinate synthetase-1. / Glazer, Evan; Kaluarachchi, Warna D.; Massey, Katheryn L.; Zhu, Cihui; Curley, Steven A.

In: Surgery, Vol. 148, No. 2, 10.05.2010, p. 310-318.

Research output: Contribution to journalArticle

Glazer, Evan ; Kaluarachchi, Warna D. ; Massey, Katheryn L. ; Zhu, Cihui ; Curley, Steven A. / Bioengineered arginase i increases caspase-3 expression of hepatocellular and pancreatic carcinoma cells despite induction of argininosuccinate synthetase-1. In: Surgery. 2010 ; Vol. 148, No. 2. pp. 310-318.
@article{38417637da6f4811a2c50252c71d4251,
title = "Bioengineered arginase i increases caspase-3 expression of hepatocellular and pancreatic carcinoma cells despite induction of argininosuccinate synthetase-1",
abstract = "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.",
author = "Evan Glazer and Kaluarachchi, {Warna D.} and Massey, {Katheryn L.} and Cihui Zhu and Curley, {Steven A.}",
year = "2010",
month = "5",
day = "10",
doi = "10.1016/j.surg.2010.03.022",
language = "English (US)",
volume = "148",
pages = "310--318",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "2",

}

TY - JOUR

T1 - Bioengineered arginase i increases caspase-3 expression of hepatocellular and pancreatic carcinoma cells despite induction of argininosuccinate synthetase-1

AU - Glazer, Evan

AU - Kaluarachchi, Warna D.

AU - Massey, Katheryn L.

AU - Zhu, Cihui

AU - Curley, Steven A.

PY - 2010/5/10

Y1 - 2010/5/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77955300014&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955300014&partnerID=8YFLogxK

U2 - 10.1016/j.surg.2010.03.022

DO - 10.1016/j.surg.2010.03.022

M3 - Article

VL - 148

SP - 310

EP - 318

JO - Surgery

JF - Surgery

SN - 0039-6060

IS - 2

ER -