Molecular basis of the potential of mesalazine to prevent colorectal cancer

Stolfi, Carmine; Pellegrini, Roberto; Franzè, Eleonora; Pallone, Francesco; Monteleone, Giovanni

doi:10.3748/wjg.14.4434

Cited by 32 publications

(34 citation statements)

References 58 publications

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“…Interestingly, a retrospective study of patients with ulcerative colitis showed that those who were not on long-term SSZ or 5-aminosalicylic acid (5-ASA) therapy (the active moiety of SSZ) were significantly more likely to develop colorectal cancer than their compliant counterparts [44]. Both epidemiological and experimental observations suggest that SSZ or 5-ASA (mesalazine) can reduce the incidence of colitis-associated CRC [44][45][46]. Our current study nevertheless demonstrates the biochemical mechanism of the combination effect of SSZ and CDDP in CRC.…”

Section: Discussionmentioning

confidence: 97%

Xc− inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism

et al. 2015

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Section: Discussionmentioning

confidence: 97%

Xc− inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism

et al. 2015

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“…In recent years, both in vitro and in vivo studies have shown that mesalamine inhibits multiple biological pathways that sustain colon cancer cell growth, thereby reducing the risk of developing inflammatory bowel disease-related colon cancer (20)(21)(22). However, the antineoplastic effects of mesalamine are seen only with doses that are not always reached in the gut following oral administration of the drug (23,24).…”

Section: Introductionmentioning

confidence: 99%

2-Methoxy-5-Amino-N-Hydroxybenzamide Sensitizes Colon Cancer Cells to TRAIL-Induced Apoptosis by Regulating Death Receptor 5 and Survivin Expression

Stolfi

Caruso

Franzè

et al. 2011

Molecular Cancer Therapeutics

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TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis is a crucial event in the control of tumor growth. However, many cancer cells, including colon cancer cells, are resistant to TRAIL-driven cell death. We have recently shown that 2-methoxy-5-amino-N-hydroxybenzamide (herein termed 2-14), a novel derivative of mesalamine, induces endoplasmic reticulum stress in colon cancer cells. Because endoplasmic reticulum stress-induced signals regulate the expression of molecules involved in TRAIL-driven apoptosis, we examined whether 2-14 makes colon cancer cells sensitive to TRAIL. Colon cancer cells were cultured with 2-14 and/or TRAIL. Death receptor (DR) 4/DR5 were analyzed by real-time PCR and flow cytometry. TRAIL pathway-associated proteins and extracellular signal-regulated kinase (ERK) were assessed by Western blotting. The in vivo capability of 2-14 to sensitize colon cancer cells to TRAIL-induced apoptosis was evaluated in a syngenic colon cancer model in which CT26-derived grafts were induced in mice. 2-14 promoted ERK-dependent induction of DR5, thereby enhancing TRAIL-mediated caspase-8 activation and apoptosis. Analysis of TRAIL-related pro-and antiapoptotic factors and functional studies revealed that survivin is involved in the protection of colon cancer cells against TRAIL-driven apoptosis. Notably, 2-14 enhanced ubiquitination and proteasome-mediated degradation of survivin. These data were confirmed in a murine model of TRAIL-resistant colon cancer in which 2-14 upregulated DR5, reduced survivin expression, and synergized with TRAIL in inhibiting tumor growth. Similarly, intraperitoneal administration of 2-14 to mice upregulated DR5 and downregulated survivin in a model of colitis-associated colon cancer. These findings indicate that 2-14 acts as a sensitizer for TRAIL-induced apoptosis and suggest that 2-14 can be useful in the therapy for TRAIL-resistant colon cancer. Mol Cancer Ther; 10(10); 1969-81. Ó2011 AACR.

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“…5-ASA reduces oxidative stress, inhibits cell proliferation and promotes apoptosis (Gasche, 2004;Stolfi et al, 2008b). At the molecular level, 5-ASA inhibits COX-2 (Peskar et al, 1987;Stolfi et al, 2008a), decreases transcriptional activity of NF-kB by modulating phosphorylation of RelA/p65 and interferes with Wnt pathway through protein phosphatase 2A (Egan et al, 1999;Bos et al, 2006).…”

Section: Conclusion and Implications For Therapy And Prophylaxismentioning

confidence: 99%

Inflammatory bowel disease and intestinal cancer: a paradigm of the Yin–Yang interplay between inflammation and cancer

Danese¹,

2010

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Colon cancer represents a paradigm for the connection between inflammation and cancer in terms of epidemiology and mechanistic studies in preclinical models. Key components of cancer promoting inflammation include master transcription factors (for example, nuclear factor jB, STAT3), proinflammatory cytokines (for example, tumor necrosis factor, interleukin-6 (IL-6)), cyclooxygenase-2 and selected chemokines (for example, CCL2). Of no less importance are mediators that keep inflammation in check, including IL-10, transforming growth factorb, toll-like receptor and the IL-1 receptor inhibitor TIR8/ SIGIRR, and the chemokine decoy and scavenger receptor D6. Dissection of molecular pathways involved in colitis-associated cancer may offer opportunities for innovative therapeutic strategies.

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Molecular basis of the potential of mesalazine to prevent colorectal cancer

Cited by 32 publications

References 58 publications

Xc− inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism

Xc− inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism

2-Methoxy-5-Amino-N-Hydroxybenzamide Sensitizes Colon Cancer Cells to TRAIL-Induced Apoptosis by Regulating Death Receptor 5 and Survivin Expression

Inflammatory bowel disease and intestinal cancer: a paradigm of the Yin–Yang interplay between inflammation and cancer

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