Laleh Arzi1, Reyhane Hoshyar2, Nazli Jafarzadeh3, Gholamhossein Riazi4, Majid Sadeghizadeh5. 1. Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran. 2. Microbiology and Molecular Genetics Department, Michigan State University, East Lansing, MI 48824, USA; Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran. 3. Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, Iran. 4. Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran. Electronic address: ghriazi@ut.ac.ir. 5. Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: sadeghma@modares.ac.ir.
Abstract
AIM: To determine the anti-metastatic potential of combinations of two bioactive carotenoids of saffron, crocin and crocetin, on 4T1 breast cancer and on a mice model of TNBC, and assess the effect of the most potent combination on the Wnt/β-catenin pathway. MAIN METHODS: The effects of the carotenoid combinations on the viability of 4T1 cells were determined by MTT assay. The effects of the nontoxic doses on migration, mobility, invasion and adhesion to ECM were examined by scratch assay, Transwell/Matrigel-coated Transwell chamber and adhesion assay respectively. Tumors were inoculated by injecting mice with 4T1 cells. The weights and survival rates of the mice and tumor sizes were monitored. Histological analysis of the tissues was conducted. The expression levels of Wnt/β-catenin pathway genes were measured by Real-time PCR and western blotting. KEY FINDINGS: Treatment of 4T1 cells with combination doses inhibited viability in a dose-dependent manner. The nontoxic combinations significantly inhibited migration, cell mobility and invasion, also attenuating adhesion to ECM. The combination therapy mice possessed more weight, higher survival rates and smaller tumors. Histological examination detected remarkably fewer metastatic foci in their livers and lungs. It was also demonstrated that the combinations exerted anti-metastatic effects by disturbing the Wnt/β-catenin target genes in the liver and tumors. SIGNIFICANCE: Our findings propose a carotenoid combination as an alternative potent herbal treatment for TNBC, which lacks the adverse effects associated with either chemotherapeutic agents or herb-chemotherapeutic drugs.
AIM: To determine the anti-metastatic potential of combinations of two bioactive carotenoids of saffron, crocin and crocetin, on 4T1breast cancer and on a mice model of TNBC, and assess the effect of the most potent combination on the Wnt/β-catenin pathway. MAIN METHODS: The effects of the carotenoid combinations on the viability of 4T1 cells were determined by MTT assay. The effects of the nontoxic doses on migration, mobility, invasion and adhesion to ECM were examined by scratch assay, Transwell/Matrigel-coated Transwell chamber and adhesion assay respectively. Tumors were inoculated by injecting mice with 4T1 cells. The weights and survival rates of the mice and tumor sizes were monitored. Histological analysis of the tissues was conducted. The expression levels of Wnt/β-catenin pathway genes were measured by Real-time PCR and western blotting. KEY FINDINGS: Treatment of 4T1 cells with combination doses inhibited viability in a dose-dependent manner. The nontoxic combinations significantly inhibited migration, cell mobility and invasion, also attenuating adhesion to ECM. The combination therapy mice possessed more weight, higher survival rates and smaller tumors. Histological examination detected remarkably fewer metastatic foci in their livers and lungs. It was also demonstrated that the combinations exerted anti-metastatic effects by disturbing the Wnt/β-catenin target genes in the liver and tumors. SIGNIFICANCE: Our findings propose a carotenoid combination as an alternative potent herbal treatment for TNBC, which lacks the adverse effects associated with either chemotherapeutic agents or herb-chemotherapeutic drugs.
Authors: Lenka Koklesova; Alena Liskova; Marek Samec; Kevin Zhai; Mariam Abotaleb; Milad Ashrafizadeh; Aranka Brockmueller; Mehdi Shakibaei; Kamil Biringer; Ondrej Bugos; Masoud Najafi; Olga Golubnitschaja; Dietrich Büsselberg; Peter Kubatka Journal: Biomolecules Date: 2020-12-10