Table 3 Current progress of pre-clinical studies of peg-arg I as anti-cancer agent
From: Drug-induced amino acid deprivation as strategy for cancer therapy
Cancer type tested | Progress | References |
|---|---|---|
Hepatocellular carcinoma (HCC) | 1. Suppressed HCC cell growth and induced apoptosis in vitro | |
2. Suppressed OTC-deficient tumor growth in athymic nude mice | ||
Acute myeloid leukemia (AML) | 1. Induced necrotic cell death in AML cell lines and some AML patient samples in vitro and in vivo (implantation of HL-60 cell line in to NOD/SCID γ mice through tail vein) | [154] |
2. Peg-arg I + cytarabine enhanced cytotoxicity in AML cell lines and AML patient samples in vitro | ||
Acute lymphoblastic leukemia (ALL) | 1. Induced apoptosis in T-lineage ALL (T-ALL) cell lines in vitro | |
2. Peg-arg I + cytarabine therapy induced T- ALL cell apoptosis in vivo (Peg-arg I monotherapy did not prolong the survival of T-ALL bearing in NOD-SCID mice) | ||
3. MSCs protected T-lineage ALL cell lines from peg-arg I cytotoxicity via soluble factors in vitro, pre-treating MSCs with vincristine may suppress such stromal protection | ||
4. eIF2α phosphorylation sensitized T-ALL cells to peg-arg I cytotoxicity in NOD-SCID mice | ||
Glioblastoma | 1. Induced ASS1-dependent non-apoptotic cell death which may be enhanced by autophagy inhibitor CQ in glioblastoma cell lines in vitro | [174] |
Melanoma | 1. Induced S and G2/M phases cell cycle arrest and apoptosis in melanoma cell line A375 in vitro | [175] |
2. Suppressed s.c. implanted melanoma in athymic nude mice | ||
Prostate cancer | Induced autophagic cell death in OTC-ve cells in vitro | [176] |
Pancreatic cancer | 1. Induced apoptosis in pancreatic cancer cell line Panc-1 in vitro | [172] |
2. Suppressed tumor growth in a s.c. implanted pancreatic cancer in athymic mice model | ||
Mesothelioma | 1. Suppressed growth of different cell lines in vitro and in vivo (s.c. implanted mesothelioma in athymic nude mouse model) | [148] |
2.Induced apoptosis and G1 arrest in mesothelioma cells in vivo | ||
3. Peg-arg I, cispatin and premetrexed did not show synergistic effect against mesothelioma growth in vivo | ||
4. Peg-arg I depleted serum and intratumoral arginine, and was internalized in mesothelioma cells in vivo |