Thymoquinone potentiates chemoprotective effect of Vitamin D3 against colon cancer: a pre-clinical finding.
Prevention of colon cancer among high-risk group has been long lasting research goal. Emerging data have evidenced the anticancer activities of Vitamin D3 (Vit.D) and Thymoquinone (TQ). The aim of the current study was to evaluate the synergistic potential of Thymoquinone and Vitamin D3 in the control of colon cancer progression using azoxymethane-induced rat model. Vit.D and TQ were given individually or in combination 4 week prior to induction and continued for a total of 20 week. At the end of the study, all animals were euthanized and their resected colons were examined macroscopically and microscopically for tumor growth. Colonic tissue preparations were used for measuring gene expression and/or protein levels of selected pro and anti-tumor biomarkers using quantitative RT-PCR, ELISA and immunohistochemistry. Compared with their individual supplementation, combined Vit.D/TQ showed prominent anti-tumor effect manifested by significant reduction (P < 0.05) of the numbers of grown tumors and large aberrant crypts foci. Mechanistically, gene expression and/or protein quantification studies revealed that combined Vit.D/TQ supplementation induced significant reduction (P < 0.01 and P < 0.05) of pro-cancerous molecules (Wnt, β-catenin, NF-κB, COX-2, iNOS, VEGF and HSP-90) as well as significant increase (P < 0.01 and P < 0.05, respectively) of anti-tumorigenesis biomarkers (DKK-1, CDNK-1A, TGF-β1, TGF-β/RII and smad4) as compared to un-supplemented or individually supplemented groups, respectively. In conclusion, TQ augmented the chemopreventive effect of Vit.D during the initiation phase of colon cancer in rat model, with the potential to suppress progression of pre-neoplastic lesions in colon carcinogenesis.
Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura UniversityMakkah, Kingdom of Saudi Arabia; Clinical Laboratory Diagnosis, Department of Animal Medicine, Faculty of Veterinary Medicine, Assiut UniversityAssiut, Egypt.
Amr M
AM
Mohamed
Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University Makkah, Kingdom of Saudi Arabia.
Bassem A
BA
Refaat
Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura UniversityMakkah, Kingdom of Saudi Arabia; Department of Pharmacology, Faculty of Medicine, Assiut UniversityAssiut, Egypt.
Adel G
AG
El-Shemi
Department of Clinical Nutrition, Faculty of Applied Medical Sciences, Umm Al-Qura University Makkah, Kingdom of Saudi Arabia.
Osama A
OA
Kensara
Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University Makkah, Kingdom of Saudi Arabia.
Jawwad
J
Ahmad
Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University Makkah, Kingdom of Saudi Arabia.
Shakir
S
Idris
Colon cancer; Vitamin D3; azoxymethane-induced rat model; thymoquinone; tumor biomarkers