Rectal and colonic mesalazine concentration in ulcerative colitis: oral vs. oral plus topical treatment

Frieri, Giuseppe; Pimpo, M.T.; Palumbo, Giancarlo; Onori, L.; Viscido, Angelo; Latella, Giovanni; Galletti, B.; Pantaleoni, Giancarlo; Caprilli, R.

doi:10.1046/j.1365-2036.1999.00642.x

Cited by 91 publications

(61 citation statements)

References 21 publications

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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). Therefore, we developed several derivatives of mesalamine and selected 2-14 as it was the more potent inhibitor of colon cancer cell growth (25).…”

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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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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“…Importantly, attenuation of p-EGFR is obtained with 5-ASA concentrations, which are reached within the gut tissue under standard oral treatment. 21,22 The effect of 5-ASA on p-EGFR is reversible and associates with no induction of cell death. In contrast to our data, two different groups have recently shown that 5-ASA promotes apoptosis of adherent HT-29 cells.…”

Section: Discussionmentioning

confidence: 99%

“…To this end, CRC cell lines were either left untreated or treated with physiological doses of 5-ASA, and then p-EGFR assessed by Western blotting. Immunoblot analysis of lysates of CRC cells showed a dramatic reduction in the constitutive level of p-EGFR after culture with physiological concentrations of 5-ASA (Figure 1a), 21,22 and this was evident in each of the four CRC cell lines used (not shown).…”

Section: -Asa Inhibits the Activation Of Egfr In Colon Cancer Cellsmentioning

confidence: 96%

Silencing of SH-PTP2 defines a crucial role in the inactivation of epidermal growth factor receptor by 5-aminosalicylic acid in colon cancer cells

et al. 2005

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Recent studies have suggested that 5-aminosalicylic acid (5-ASA) inhibits colorectal cancer (CRC) development. However, the mechanism underlying the antineoplastic effect of 5-ASA remains unknown. We here examined the effect of 5-ASA on epidermal growth factor receptor (EGFR) activation, a pathway that triggers mitogenic signals in CRC cells. We show that 5-ASA inhibits EGFR activation, through a mechanism that does not rely on CRC cell death induction. 5-ASA enhances the activity, but not expression, of phosphorylated (p)-EGFR-targeting phosphatases (PTPs), and treatment of cells with PTP inhibitors abrogates the 5-ASA-mediated EGFR dephosphorylation. Both SH-PTP1 and SH-PTP2 interact with EGFR upon 5-ASA treatment. However, knockdown of SH-PTP2 but not SH-PTP1 by small interference RNAs prevents the 5-ASA-induced EGFR dephosphorylation. Finally, we show that 5-ASA attenuates p-EGFR in ex vivo organ cultures of CRC explants. Data indicate that 5-ASA disrupts EGFR signalling by enhancing SH-PTP2 activity, and suggest a mechanism by which 5-ASA interferes with CRC growth.

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“…[13][14][15][16] The addition of topical 5-ASA to oral therapy increases mucosal levels of mesalamine by 3-fold in the descending colon and over 20-fold in the rectum. [17] Moreover, it has been demonstrated repeatedly that the combination of 5-ASA in oral and enema formulations is superior to either therapy alone in inducing and maintaining remission of extensive colitis. [13][14][15][16][17][18] Safety of 5-ASA Therapy:-As a class, 5-ASA therapy is considered exceptionally safe.…”

Section: Induction Of Remission In Ulcerative Colitismentioning

confidence: 99%

“…[17] Moreover, it has been demonstrated repeatedly that the combination of 5-ASA in oral and enema formulations is superior to either therapy alone in inducing and maintaining remission of extensive colitis. [13][14][15][16][17][18] Safety of 5-ASA Therapy:-As a class, 5-ASA therapy is considered exceptionally safe. The side-effect profiles of mesalamine and balsalazide are similar to placebo, whereas olsalazine and sulfasalazine are associated with an increased incidence of treatment withdrawal due to adverse events.…”

Section: Induction Of Remission In Ulcerative Colitismentioning

confidence: 99%

Discussion About Treatment of Ulcerative Colitis.

alfattany¹,

sharif²,

SalemMabkhot³

et al. 2017

IJAR

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Rectal and colonic mesalazine concentration in ulcerative colitis: oral vs. oral plus topical treatment

Abstract: Topical treatment of mesalazine significantly increases mucosal concentrations of mesalazine up to the splenic flexure, supporting the rationale to treat left-sided ulcerative colitis with topical formulations of mesalazine.

Cited by 91 publications

References 21 publications

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

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

Silencing of SH-PTP2 defines a crucial role in the inactivation of epidermal growth factor receptor by 5-aminosalicylic acid in colon cancer cells

Discussion About Treatment of Ulcerative Colitis.

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