Crocin synergistically enhances the anti-proliferative activity of 5-FU through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer

Amerizadeh, Forouzan, Rezaei, Nastaran, Rahmani, Farzad, Hassanian, Seyed Mahdi, Moradi-Marjaneh, Reyhaneh, Fiuji, Hamid, Boroumand, Nadia, Nosrati-Tirkani, Abolfazl, Ghayour-Mobarhan, Majid, Ferns, Gordon A, Khazaei, Majid and Avan, Amir (2018) Crocin synergistically enhances the anti-proliferative activity of 5-FU through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer. Journal of Cellular Biochemistry, 119 (12). pp. 10250-10261. ISSN 0730-2312

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Abstract

Colorectal-cancer (CRC) is the third most common cause of cancer-related-death, and hence there is a need for the identification of novel-agents to improve the efficacy of existing-therapies. There is growing evidence for the anti-tumor-activity of crocin, although its activity and molecular-mechanisms in CRC remains to be elucidated. Here we explored the therapeutic-application of crocin or its combination with 5-Flurouracil in a mouse-model of colitis-associated colon-cancer. The anti-proliferative-activity of crocin was assessed in 2- and 3-dimensional cell-culture-models. The migratory-behaviors were determined, while the expression-levels of several-genes were assessed by qRT-PCR/Western-blotting. We examined the anti-inflammatory properties of crocin by pathological-evaluation and disease-activity-index as well as oxidative/ antioxidant markers: malondialdehyde (MDA) and total-thiols (T-SH) levels and superoxide-dismutase (SOD) and catalase (CAT) activity. Crocin suppressed cell-growth and the invasive-behavior of CRC-cells through modulation of the Wnt-pathway and E-cadherin. Moreover, administration of crocin alone, or in combination with 5-FU dramatically reduced the tumor-number and tumor-size in both distal/mid-colon followed by reduction in disease-activity-index. Crocin also suppressed the colonic-inflammation induced by Dextran-sulfate-sodium and notably recovered the increased-levels of MDA, decreased Thiol-levels and activity of CAT-levels. Crocin was able to ameliorate the severe-inflammation with mucosal-ulcers and high grade-dysplastic-crypts as detected by inflammation-score, Crypt-loss, pathological-changes and histology-scores. We demonstrated an antitumor-activity of crocin in CRC and its potential role in improvement of inflammation with mucosal ulcers and high grade dysplastic crypts, supporting the desireability of further investigations on the therapeutic potential of this approach in CRC.

Item Type: Article
Keywords: colorectal cancer; crocin; anti-tumor effect; colitis-associated colorectal cancer gastrointestinal
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Brighton and Sussex Medical School > Division of Medical Education
Depositing User: Elizabeth Renvoize
Date Deposited: 20 Jul 2018 11:59
Last Modified: 06 Dec 2018 15:51
URI: http://srodev.sussex.ac.uk/id/eprint/77287

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