DBeQ-mediated pharmacological modulation of the retrotranslocation step of ERAD may exhibit a potent therapeutic approach against colorectal cancer
Acta Pharmaceutica Sciencia, vol.61, no.4, pp.385-396, 2023 (Scopus)
- Publication Type: Article / Article
- Volume: 61 Issue: 4
- Publication Date: 2023
- Doi Number: 10.23893/1307-2080.aps6125
- Journal Name: Acta Pharmaceutica Sciencia
- Journal Indexes: Scopus, EMBASE
- Page Numbers: pp.385-396
- Keywords: Anti-tumorigenic, colon cancer, DBeQ, ER-associated degradation, p97/VCP
- Süleyman Demirel University Affiliated: Yes
Abstract
The incidence of colorectal cancer is 30% higher in men compared to women. Altho-ugh there are different treatment options for colorectal cancer, including chemot-herapy 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/Va-losin-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-associa-ted 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 anchorage-independent 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.