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

Seishima, Ryo; Okabayashi, Koji; Nagano, Osamu; Hasegawa, Hirotoshi; Tsuruta, Masashi; Shimoda, Masayuki; Kameyama, Kaori; Saya, Hideyuki; Kitagawa, Yuko

doi:10.1016/j.clinre.2015.11.007

Cited by 26 publications

(21 citation statements)

References 29 publications

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“…It is well known that the alternative splicing of CD44 pre-mRNA is a main source of the diverse CD44 isoforms, and these isoforms with different properties might have diverse effects on cancer progression. The overexpression of CD44v9 has been associated with invasive prostate cancer and gastric cancer [37][38][39]. Another study indicated that the expression of CD44v6, in sporadic gastric tumors is a potential marker to distinguish intestinal-and diffuse-type gastric adenocarcinomas [40].…”

Section: Discussionmentioning

confidence: 99%

hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing

Peng

Liu

et al. 2019

Cancer Cell Int

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Background: The high prevalence of alternative splicing among genes implies the importance of genomic complexity in regulating normal physiological processes and diseases such as gastric cancer (GC). The standard form of stem cell marker CD44 (CD44S) and its alternatives with additional exons are reported to play important roles in multiple types of tumors, but the regulation mechanism of CD44 alternative splicing is not fully understood.Methods: Here the expression of hnRNPK was analyzed among the Cancer Genome Atlas (TCGA) cohort of GC. The function of hnRNPK in GC cells was analyzed and its downstream targeted gene was identified by chromatin immunoprecipitation and dual luciferase report assay. Finally, effect of hnRNPK and its downstream splicing regulator on CD44 alternative splicing was investigated.Results: The expression of hnRNPK was significantly increased in GC and its upregulation was associated with tumor stage and metastasis. Loss-of-function studies found that hnRNPK could promote GC cell proliferation, migration, and invasion. The upregulation of hnRNPK activates the expression of the splicing regulator SRSF1 by binding to the first motif upstream the start codon (− 65 to − 77 site), thereby increasing splicing activity and expression of an oncogenic CD44 isoform, CD44E (has additional variant exons 8 to 10, CD44v8-v10). Conclusion:These findings revealed the importance of the hnRNPK-SRSF1-CD44E axis in promoting gastric tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing

Peng

Liu

et al. 2019

Cancer Cell Int

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“…Sulfasalazine was used as a reference drug to assess the efficacy of riboflavin. It is widely used to treat ulcerative colitis, most often to maintain remission …”

Section: Methodsmentioning

confidence: 99%

Ameliorative effects of riboflavin on acetic acid‐induced colonic injury in rats

Karakoyun

Ertaş

Yüksel

et al. 2017

Clin Exp Pharma Physio

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Riboflavin (RF) has been found to be a promising antioxidant and/or anti-inflammatory agent in several studies. However, the effect of RF against acetic acid (AA)-induced colonic injury is currently unknown. This study aimed to investigate the potential antioxidant and protective effects of RF in a rat model of ulcerative colitis. Starting immediately after the colitis induction (AA+RF group) or 1 week before the colitis induction (RF+AA+RF group), the rats were treated with RF (25 mg/kg per day; p.o.) for 3 days. The control and AA groups received saline (1 mL; p.o.) whereas AA+SS group (positive control) received sulfasalazine (100 mg/kg per day; p.o.) for 3 days. Colonic samples were taken for the biochemical and histological assessments on the third day. High damage scores, elevated tissue wet weight index (WI), tissue myeloperoxidase (MPO) activity, 8-hydroxy-2'-deoxyguanosine levels and chemiluminescence values, and a pronounced decrease in antioxidant glutathione (GSH) levels of the AA group were all reversed by RF pretreatment (RF+AA+RF group) and SS treatment (AA+SS group) (P < .05-.001). Tissue WI, MPO activity and GSH levels were not statistically changed in the AA+RF group. Western blot analysis revealed that the decreased protein expressions of tissue collagen (COL) 1A1, COL3A1 and transforming growth factor-β1 in the AA group were elevated in all the treatment groups (P < .05-.001). In conclusion, RF exerts both the antioxidant and anti-inflammatory effects against AA-induced colonic inflammation by suppressing neutrophil accumulation, inhibiting reactive oxidant generation, preserving endogenous glutathione, improving oxidative DNA damage and regulating inflammatory mediators, suggesting a future potential role in the treatment and prevention of ulcerative colitis.

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“…After oral administration, sulfonamides are well absorbed from the digestive tract [6]. The exceptions are sulfaguanidine (SGV) [37] and sulfasalazine (SLZ) [38] which practically cannot be absorbed. For this reason, they are used in the intestinal infections treatment.…”

Section: Pharmacokinetics Of Sulfonamidesmentioning

confidence: 99%

“…In the turtles [41] and monkeys [27], the main metabolic pathway is oxidation, wherein one or two hydroxyl groups are introduced in the position 4, 5 or 6 of sulfonamides moiety to form corresponding monohydroxy or dihydroxy metabolites. These metabolites retain a part (2.5-39.5%) of antimicrobial activity [42] of the parental sulfonamides and excrete in the urine unchanged or after conjugation with glucuronic acid or sulfate [38].…”

Section: Pharmacokinetics Of Sulfonamidesmentioning

confidence: 99%

Antimicrobial sulfonamide drugs

Tacic¹,

Nikolić²,

Nikolić³

et al. 2017

Adv techn

118

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Sulfonamides are the first successfully synthesized antimicrobial drugs. The mechanism of sulfonamides antimicrobial action involves competitive inhibition of folic acid synthesis which prevents the growth and reproduction of microorganisms. Due to this mechanism of action, sulfonamides belong to the group of bacteriostatic agents. Although they have been applied in therapy for more than 70 years, sulfonamides are still the drugs of choice for the treatment of several conditions and diseases. A wider sulfonamides application in the therapy is limited by bacterial resistance and sulfonamides side effects. Antimicrobial sulfonamides and their metabolites are classified as persistent organic pollutants. For sulfonamides degradation and removal from the environment, various techniques can be applied such as different oxidation techniques, including chlorination and advanced oxidation processes, adsorption processes, membrane processes and combined processes.

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

Cited by 26 publications

References 29 publications

hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing

hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing

Ameliorative effects of riboflavin on acetic acid‐induced colonic injury in rats

Antimicrobial sulfonamide drugs

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