Phytic acid potentiates oxaliplatin effects in colorectal cancer induced by 1,2-DMH: the role of miR-224 and miR-200a

Tarek M Okda; Mohamed A Katry; Noha M Ragab; Abdel-Gawad S Shalkami

doi:10.5114/wo.2021.106061

Phytic acid potentiates oxaliplatin effects in colorectal cancer induced by 1,2-DMH: the role of miR-224 and miR-200a

Contemp Oncol (Pozn). 2021;25(2):118-124. doi: 10.5114/wo.2021.106061. Epub 2021 May 13.

Authors

Tarek M Okda¹, Mohamed A Katry^{2

3}, Noha M Ragab⁴, Abdel-Gawad S Shalkami⁵

Affiliations

¹ Department of Biochemistry, Faculty of Pharmacy, Damanhour University, Egypt.
² Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhour University, Egypt.
³ Department of Oral Biology and Diagnostic Sciences, Augusta University, Augusta, USA.
⁴ Department of Pathology, Medical Research Institute, Alexandria University, Egypt.
⁵ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Egypt.

Abstract

Introduction: The third most frequently diagnosed cancer and one of the highest causes of tumour deaths worldwide is colorectal cancer (CRC). The main objective of this study was to determine the role of microRNA-224 (miR-224) as well as microRNA-200a (miR-200a) in CRC. Phytic acid (PA) is a natural antitumour product that was reported to inhibit CRC and play a vital role as a chemopreventive agent against CRC.

Material and methods: We induced CRC in albino rats using 1,2-dimethylhydrazine (1,2-DMH). The miR-224, miR-200a, and β-catenin expressions were determined. ELISAs were performed to investigate Bcl-2 expression, caspase-3 activity, and total tissue antioxidants. Finally, histopathological investigations were performed.

Results: We observed a chemoprotective role of PA. PA has a synergistic effect as an antitumour agent with oxaliplatin in CRC treatment. The miR-224, miR-200a, and β-catenin expression, when treated with PA alone or with oxaliplatin, was decreased markedly in comparison with the positive control group. The histopathological investigations of colorectal tissues confirmed our molecular and biochemical findings.

Conclusions: Phytic acid possessed efficient anti-carcinogenic properties alone or with oxaliplatin against 1,2-DMH-induced CRC in rats through pathways of apoptosis, cell proliferation, and antioxidants.

Keywords: CRC; miR-200a; miR-224; oxaliplatin; phytic acid.