DBEQ-MEDIATED PHARMACOLOGICAL MODULATION OF THE RETROTRANSLOCATION STEP OF ERAD MAY EXHIBIT A POTENT THERAPEUTIC APPROACH AGAINST COLORECTAL CANCER

YALCİN ERZURUMLU, HATİCE KUBRA DOGAN

Acta Pharmaceutica Sciencia - 2023;61(4):385-396

Department of Biochemistry, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Türkiye

 

DOI : 10.23893/1307-2080.APS6125 The incidence of colorectal cancer is 30% higher in men compared to women. Although there are different treatment options for colorectal cancer, including chemotherapy and immunotherapy, acquired drug resistance and some specific mutations substantially restrict the treatment options. N(2), N(4)-dibenzylquinazoline-2,4- diamine (DBeQ) is a selective and ATP-competitive inhibitor molecule of p97/Valosin- containing protein (VCP) protein. p97/VCP is a well-conserved and abundant hexameric type II ATPases associated with diverse cellular activities (AAA+) type ATPases protein. It functions as an ATP-dependent segregase and plays a role in various cellular processes, such as autophagy and endoplasmic reticulum-associated degradation (ERAD). Herein, we evaluated the therapeutic potential of DBeQ on colorectal cancer cells, Caco-2 and HT-29. Our data indicated that DBeQ treatment strongly reduced the proliferative capacity, colonial growth and anchorageindependent growth of colorectal cancer cells. Moreover, DBeQ strongly increased cytochrome-c and CCAAT-enhancer-binding protein homologous protein (CHOP) protein levels and also induced cleaved caspase-3 and caspase-7 levels. Present findings suggest that DBeQ may offer a potential therapeutic effect for colorectal cancer treatment.