From: Drug-induced amino acid deprivation as strategy for cancer therapy
Cancer type tested | Progress | References |
---|---|---|
Hepatocellular carcinoma (HCC) | 1. Decreased HCC cell viability in vitro | [13] |
2. Suppressed tumor growth and prolonged survival of engrafted.c. implanted tumor-bearing SCID mice | ||
3. ASS1 + ve and OTC + ve HCC cells are resistant to ADI. | ||
Melanoma | 1. Decreased melanoma cell viability in vitro | [13] |
2. Suppressed tumor growth and prolonged survival of s.c. implanted tumor-bearing athymic nude mice | ||
Small cell lung cancer | 1. Induced autophagy and cell death in ASS1-ve cell in vitro (about 50% of samples tested in the study were ASS1-ve) | [164] |
2. Suppressed growth of s.c. implanted tumor in athymic nude mice | ||
Glioblastoma | 1. Induced autophagy and caspase independent cell death in ASS1-ve cell lines and clinical samples (approximately 30% glioblastoma samples tested in the study are ASS1-ve) | [165] |
2. Autophagy inhibitor chlorquine accelerated ADI-PEG20 induced cell death in vitro | ||
Pancreatic cancer | 1. Inhibited growth and induced apoptosis of ASS1-ve pancreatic cancer cell lines in vitro (about 80% pancreatic cancer samples tested in the study were ASS1-ve) | |
2. Suppressed growth of subcutaneously implanted tumor in athymic nude mice. | ||
3. ADI-PEG20 + gemcitabine showed enhanced cell death in gemcitabine-resistant ASS1-ve pancreatic cell line compared to ADI-PEG20 or gemcitabine only groups in vitro | ||
4. ADI-PEG20 + gemcitabine enhanced growth suppression in s.c. implanted gemcitabine-resistant ASS1-ve tumor in athymic nude mice. | ||
Acute myeloid leukemia (AML) | 1. Induced primary AML apoptosis in vitro | [137] |
2. Reduced AML burden in NOD-SCID mice | ||
3. ADI-PEG20 + cytarabine further enhanced AML clearance | ||
Prostate cancer | 1. Induced autophagy, mitochondrial dysfunction, DNA leakage and caspase-independent cell death in a prostate cancer cell line in vitro | |
2. Autophagy inhibitor chloroquine enhanced and accelerated ADI-PEG20 induced prostate cancer cell death in vitro | ||
3. ADI-PEG20 + docetaxel showed enhanced tumor suppression in s.c. implanted tumor in athymic nude mice | ||
Bladder cancer | 1. Induced caspase-independent apoptosis and autophagy in bladder cancer cell lines in vitro and reduced tumor growth and in vivo (s.c. implanted tumor in athymic nude mice) | |
2. ASS1-ve due to methylation may be related poor prognosis clinically, and linked to invasion and enhanced invasion and proliferation in bladder cancer cells in vitro | ||
3. Inhibited pyrimidine metabolism by reducing protein level of thymidylate synthase, dihydro-folate reductase and thymidine kinase 1 and enhanced cytotoxicity in ASS1-methylated bladder cancer cell lines in vitro and in vivo (s.c. implanted tumor in CD1 nude mice) | ||
Breast cancer | Induced mitochondrial damage and autophagy-dependent cell death in ASS1-ve breast cancer cell in vitro | [171] |