Crocin Potentiates Anti-tumor Properties of 5-FU by Regulating Cell Proliferation and Tumor Necrosis in Breast Cancer

Author:

Rezaei Nastaran1,Al-Asady Abdulridha Mohammed23,Hashemzehi Milad1,Moradi Binabaj Maryam45,Rahmani Farzad467,Avan Amir7,Eskandari Moein4,Jalili-Nik Mohammad4,Asgharzadeh Fereshteh1,Nazari Seyedeh Elnaz1,Ryzhikov Mikhail89,Khazaei Majid7,Hassanian Seyed Mahdi47

Affiliation:

1. Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2. Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3. Department of Medical Sciences, Faculty of Nursing, University of Warith Al-Anbiyaa, Iraq

4. Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5. Non-Communicable Diseases Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

6. Kashmar School of Nursing, Mashhad University of Medical Sciences, Mashhad, Iran

7. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

8. Saint Louis University, School of Medicine, St. Louis, MO, USA

9. Medical School, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Introduction:: Breast cancer is one of the most prevalent malignancies among women around the world. Crocus sativus, a natural food coloring and flavoring, has potent anti-tumor properties. The aim of the current study was to investigate the therapeutic potential of crocin, the main pharmacological active component of saffron, either alone or in combination with the standard chemotherapeutic treatment, 5-FU, in Breast cancer (BC) progression in both cellular and animal models. Material and Methods: MTT, Real-Time PCR, Western Blotting, Hematoxylin and eosin (H&E) tissue staining were applied to determine the anti-tumor properties of crocin in in vitro and in vivo samples. Results:: Our findings showed that crocin decreased breast cancer cell proliferation by suppressing cyclin D1 expression and Wnt/β-catenin signaling activation. Moreover, this molecule improved 5- FU anti-cancer activities by decreasing the tumor volume and weight, increasing tumor necrosis, and suppressing tumor inflammation in an animal model. Inflammation-associated anti-cancer activity of crocin is mediated by the down-regulation of pro-inflammatory genes, including IFN-γ and IL-1β, as well as inhibition of oxidative stress responses within the tumor environment. Conclusion:: This is the first study demonstrating the potent anti-tumor properties of crocin against BC progression. Our results suggest that this effective and low-toxic molecule could be a promising agent for reducing BC tumor progression when administered either alone or in combination with standard treatment in breast cancer patients.

Publisher

Bentham Science Publishers Ltd.

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