Sulfasalazine, a therapeutic agent for ulcerative colitis, inhibits the growth of CD44v9(+) cancer stem cells in ulcerative colitis-related cancer

Clinics and Research in Hepatology and Gastroenterology
Ryo SeishimaYuko Kitagawa

Abstract

Sulfasalazine reduces the risk of ulcerative colitis (UC)-related cancer through its anti-inflammatory effect and induction of oxidative stress in cancer cells by inhibiting the glutamate-cystine transporter, which is closely associated with the cancer stem cell surface marker CD44v9. This study aimed to quantify the effects of sulfasalazine on CD44v9 expression and pathological factors in colorectal cancers (CRCs) arising from UC. Twenty-six patients with UC-related cancer were classified into groups according to the length of sulfasalazine treatment as follows: (1) long-term (LT) (≥ 5 years) and (2) short-term (ST) (< 5 years). Using immunohistochemistry, we compared CD44v9 and Ki-67 expression and pathological characteristics of each group's tumors. In vitro assay was performed to investigate the effect of sulfasalazine on epithelial differentiation and proliferation of CD44(+) cancer cells. Immunohistochemical analysis revealed that CD44v9 expression tended to be lower in the LT group (LT:ST=15.4%:46.2%, P=0.20), and Ki-67/CD44v9 double-stained cells were significantly lower in the LT group (LT:ST=0%:6.9%, P=0.01). Pathologically, the frequency of well-differentiated adenocarcinomas was higher in the LT group (LT:ST=84.6%:3...Continue Reading

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Citations

Nov 23, 2017·Clinical and Experimental Pharmacology & Physiology·Berna KarakoyunGöksel Şener
Dec 21, 2019·Cancer Cell International·Wei-Zhao PengJian-Zheng Jie
Oct 19, 2017·Cancer Research·Fumiyasu OkazakiHideto To
Dec 10, 2020·Journal of Clinical Biochemistry and Nutrition·Young-Min HanKi Baik Hahm
Sep 18, 2021·Molecular Carcinogenesis·Carly S WilderJohn DiGiovanni

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