Chemotherapeutic potential of betanin/capecitabine combination targeting colon cancer: experimental and bioinformatic studies exploring NFκB and cyclin D1 interplay

Rehab Ahmed; Sawsan A Zaitone; Asmaa K K Abdelmaogood; Huda M Atef; Mona F M Soliman; Alaa M Badawy; Howaida S Ali; AbdelNaser Zaid; Hatem I Mokhtar; Lamiaa M Elabbasy; Emad Kandil; Asmaa Mokhtar Yosef; Rama I Mahran

doi:10.3389/fphar.2024.1362739

Chemotherapeutic potential of betanin/capecitabine combination targeting colon cancer: experimental and bioinformatic studies exploring NFκB and cyclin D1 interplay

Front Pharmacol. 2024 Apr 5:15:1362739. doi: 10.3389/fphar.2024.1362739. eCollection 2024.

Authors

Rehab Ahmed^{1

2}, Sawsan A Zaitone^{3

4}, Asmaa K K Abdelmaogood⁵, Huda M Atef⁶, Mona F M Soliman^{7

8}, Alaa M Badawy⁹, Howaida S Ali^{10

11}, AbdelNaser Zaid^{12

13}, Hatem I Mokhtar¹⁴, Lamiaa M Elabbasy^{15

16}, Emad Kandil¹⁶, Asmaa Mokhtar Yosef¹⁷, Rama I Mahran¹⁸

Affiliations

¹ Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
² Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan.
³ Department of Pharmacology & Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
⁴ Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
⁵ Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
⁶ Department of Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁷ Department of Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁸ Department of Medical Histology and Cell Biology, Faculty of Medicine, Horus University, New Damiettta, Egypt.
⁹ Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
¹⁰ Department of Pharmacology, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia.
¹¹ Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.
¹² Department of Surgery, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia.
¹³ Department of General Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt.
¹⁴ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sinai University-Kantara Branch, Ismailia, Egypt.
¹⁵ Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
¹⁶ Department of Basic Medical Sciences, College of Medicine, Almaarefa University, Riyadh, Saudi Arabia.
¹⁷ PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
¹⁸ Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.

Abstract

Introduction: Betanin (C₂₄H₂₆N₂O₁₃) is safe to use as food additives approved by the FDA with anti-inflammatory and anticancer effects in many types of cancer cell lines. The current experiment was designed to test the chemotherapeutic effect of the combination of betanin with the standard chemotherapeutic agent, capecitabine, against chemically induced colon cancer in mice. Methods: Bioinformatic approach was designed to get information about the possible mechanisms through which the drugs may control cancer development. Five groups of mice were assigned as, (i) saline, (ii) colon cancer, (iii) betanin, (iv) capecitabine and (v) betanin/capecitabine. Drugs were given orally for a period of six weeks. Colon tissues were separated and used for biological assays and histopathology. Results: In addition, the mRNA expression of TNF-α (4.58-fold), NFκB (5.33-fold), IL-1β (4.99-fold), cyclin D1 (4.07-fold), and IL-6 (3.55-fold) and protein levels showed several folds increases versus the saline group. Tumor histopathology scores in the colon cancer group (including cryptic distortion and hyperplasia) and immunostaining for NFκB (2.94-fold) were high while periodic-acid Schiff staining demonstrated poor mucin content (33% of the saline group). These pathologic manifestations were reduced remarkably in betanin/capecitabine group. Conclusion: Collectively, our findings demonstrated the usefulness of betanin/capecitabine combination in targeting colon cancer and highlighted that betanin is a promising adjuvant therapy to capecitabine in treating colon cancer patients.

Keywords: NFκB; betanin; bioinformatic study; capecitabine; cyclin D1; experimental colon cancer; mouse.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The authors extend their appreciation to the Deanship of Scientific Research at the University of Tabuk for funding this work through research no. S-1443-0193.