2. Academic Validation
  3. PRMT7 Inhibitor SGC8158 Enhances Doxorubicin-Induced DNA Damage and Its Cytotoxicity

PRMT7 Inhibitor SGC8158 Enhances Doxorubicin-Induced DNA Damage and Its Cytotoxicity

  • Int J Mol Sci. 2022 Oct 14;23(20):12323. doi: 10.3390/ijms232012323.
Ahyeon Jeong 1,  Yena Cho 1,  Minkyeong Cho 1,  Gyu-Un Bae 1,  Dae-Geun Song 2,  Su-Nam Kim 2 3,  Yong Kee Kim 1
Affiliations

Affiliations

  • 1 Muscle Physiome Research Center and Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University, Seoul 04310, Korea.
  • 2 Natural Products Research Institute, KIST Gangneung, Gangneung 25451, Korea.
  • 3 Division of Bio-Medical Science and Technology, University of Science and Technology KIST School, Seoul 02792, Korea.
PMID: 36293180 DOI: 10.3390/ijms232012323
Abstract

Protein arginine methyltransferase 7 (PRMT7) regulates various cellular responses, including gene expression, cell migration, stress responses, and stemness. In this study, we investigated the biological role of PRMT7 in cell cycle progression and DNA damage response (DDR) by inhibiting PRMT7 activity with either SGC8158 treatment or its specific siRNA transfection. Suppression of PRMT7 caused cell cycle arrest at the G1 phase, resulting from the stabilization and subsequent accumulation of p21 protein. In addition, PRMT7 activity is closely associated with DNA repair pathways, including both homologous recombination and non-homologous end-joining. Interestingly, SGC8158, in combination with doxorubicin, led to a synergistic increase in both DNA damage and cytotoxicity in MCF7 cells. Taken together, our data demonstrate that PRMT7 is a critical modulator of cell growth and DDR, indicating that it is a promising target for Cancer treatment.

Keywords

DNA damage response; SGC8158; cell cycle; protein arginine methyltransferase 7; senescence.

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