ArticleBMC cancer2014
Arginine deiminase augments the chemosensitivity of argininosuccinate synthetase-deficient pancreatic cancer cells to gemcitabine via inhibition of NF-κB signaling.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Extract ofToxins · 2025Article
- Synergistic effects of L-arginine and argininosuccinate synthetase 1 in inducing apoptosis in hepatocellular carcinoma.Journal of liver cancer · 2025Article
- Enhanced anti-cancer efficacy of arginine deaminase expressed by tumor-seeking Salmonella Gallinarum.Oncogene · 2024Article
- Metabolic responses to the occurrence and chemotherapy of pancreatic cancer: biomarker identification and prognosis prediction.Scientific reports · 2024Article
- Targeting cancer metabolic pathways for improving chemotherapy and immunotherapy.Cancer letters · 2023Review
- Human arginase I: a potential broad-spectrum anti-cancer agent.3 Biotech · 2023Review
- Mucosal microbiome associates with progression to gastric cancer.Theranostics · 2022Article
- Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma.International journal of molecular sciences · 2021Review
- Arginine Deiminase Induces Immunogenic Cell Death and Is Enhanced byMolecules (Basel, Switzerland) · 2021Article
- Genome-wide CRISPR/Cas9 knockout screening uncovers a novel inflammatory pathway critical for resistance to arginine-deprivation therapy.Theranostics · 2021Article
- Arginine deprivation inhibits pancreatic cancer cell migration, invasion and EMT via the down regulation of Snail, Slug, Twist, and MMP1/9.Journal of physiology and biochemistry · 2020Article
- Histone deacetylase inhibition is synthetically lethal with arginine deprivation in pancreatic cancers with low argininosuccinate synthetase 1 expression.Theranostics · 2020Article
- Review
- Yarrow supercritical extract exerts antitumoral properties by targeting lipid metabolism in pancreatic cancer.PloS one · 2019Article
- Decreased argininosuccinate synthetase expression in Thai patients with cholangiocarcinoma and the effects of ADI-PEG20 treatment in CCA cell lines.Oncology letters · 2018Article
- Drug-induced amino acid deprivation as strategy for cancer therapy.Journal of hematology & oncology · 2017Review
- Article
- Reduced argininosuccinate synthetase expression in refractory sarcomas: Impacts on therapeutic potential and drug resistance.Oncotarget · 2016Article
- Review
- Arginine Metabolism in Bacterial Pathogenesis and Cancer Therapy.International journal of molecular sciences · 2016Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic cancer is a leading cause of cancer-related deaths in the world with a 5-year survival rate of less than 6%. Currently, there is no successful therapeutic strategy for advanced pancreatic cancer, and new effective strategies are urgently needed. Recently, an arginine deprivation agent, arginine deiminase, was found to inhibit the growth of some tumor cells (i.e., hepatocellular carcinoma, melanoma, and lung cancer) deficient in argininosuccinate synthetase (ASS), an enzyme used to synthesize arginine. The purpose of this study was to evaluate the therapeutic efficacy of arginine deiminase in combination with gemcitabine, the first line chemotherapeutic drug for patients with pancreatic cancer, and to identify the mechanisms associated with its anticancer effects.
methodsIn this study, we first analyzed the expression levels of ASS in pancreatic cancer cell lines and tumor tissues using immunohistochemistry and RT-PCR. We further tested the effects of the combination regimen of arginine deiminase with gemcitabine on pancreatic cancer cell lines in vitro and in vivo.
resultsClinical investigation showed that pancreatic cancers with reduced ASS expression were associated with higher survivin expression and more lymph node metastasis and local invasion. Treatment of ASS-deficient PANC-1 cells with arginine deiminase decreased their proliferation in a dose- and time-dependent manner. Furthermore, arginine deiminase potentiated the antitumor effects of gemcitabine on PANC-1 cells via multiple mechanisms including induction of cell cycle arrest in the S phase, upregulation of the expression of caspase-3 and 9, and inhibition of activation of the NF-κB survival pathway by blocking NF-κB p65 signaling via suppressing the nuclear translocation and phosphorylation (serine 536) of NF-κB p65 in vitro. Moreover, arginine deiminase can enhance antitumor activity of gemcitabine-based chemotherapy in the mouse xenograft model.
conclusionsOur results suggest that arginine deprivation by arginine deiminase, in combination with gemcitabine, may offer a novel effective treatment strategy for patients with pancreatic cancer and potentially improve the outcome of patients with pancreatic cancer.
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