Inhibition of protein arginine deiminase II suppresses retinoblastoma in orthotopic transplantation in mice
Copyright policy )Inhibition of protein arginine deiminase II suppresses retinoblastoma in orthotopic transplantation in mice
Chemotherapies are used for treating retinoblastoma; however, numerous patients suffer from recurrence or symptoms due to chemotherapy, which emphasizes the need for alternative therapeutic strategies. The present study demonstrated that protein arginine deiminase Ⅱ (PADI2) was highly expressed in human and mouse retinoblastoma tissues due to the overexpression of E2 factor (E2F). By inhibiting PADI2 activity, the expression of phosphorylated AKT was reduced, and cleaved poly (ADP‑ribose) polymerase level was increased, leading to induced apoptosis. Similar results were obtained in orthotopic mouse models with reduced tumor volumes. In addition, BB‑Cl‑amidine showed low toxicity in vivo. These results suggested that PADI2 inhibition has potential clinical translation. Furthermore, the present study highlights the potential of epigenetic approaches to target RB1‑deficient mutations at the molecular level. The current findings provide new insights into the importance of retinoblastoma intervention by managing PADI2 activity according to the treatment of specific inhibitors and depletion approaches in vitro and in orthotopic mouse models.
- GRADUATE SCHOOL
- Seoul National University Korea (Republic of)
- Yonsei University College of Medicine
- Yonsei University Medical Library Korea (Republic of)
- BIOMEDICAL RESEARCH INSTITUTE
AKT phosphorylation, E2 factor, Animals OR Disease Models, Retinal Neoplasms, Retinoblastoma, 610, Articles, BB‑Cl‑amidine, retinoblastoma, Mice, Disease Models, Animal, protein arginine deiminase II, Animal OR Humans OR Mice OR Mutation OR Protein-Arginine Deiminases / genetics OR Protein-Arginine Deiminases / metabolism OR Retinal Neoplasms* / drug therapy OR Retinal Neoplasms* / genetics OR Retinoblastoma* / drug therapy OR Retinoblastoma* / genetics OR Retinoblastoma* / pathology, Mutation, Protein-Arginine Deiminases, Humans, Animals
AKT phosphorylation, E2 factor, Animals OR Disease Models, Retinal Neoplasms, Retinoblastoma, 610, Articles, BB‑Cl‑amidine, retinoblastoma, Mice, Disease Models, Animal, protein arginine deiminase II, Animal OR Humans OR Mice OR Mutation OR Protein-Arginine Deiminases / genetics OR Protein-Arginine Deiminases / metabolism OR Retinal Neoplasms* / drug therapy OR Retinal Neoplasms* / genetics OR Retinoblastoma* / drug therapy OR Retinoblastoma* / genetics OR Retinoblastoma* / pathology, Mutation, Protein-Arginine Deiminases, Humans, Animals
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