Objective: With increasing incidence of cancers globally and limited resources in some affected countries, repurposing existing drugs for reducing tumorigenesis is highly important. Artemisinin and caffeine have potent anti-oxidative and anti-tumor properties but are therapies for other diseases. This study evaluated the biochemical and p53 gene modulatory effects of doses of artemisinin-caffeine combination on breast, lungs and liver tissues in rats induced with DMBA. Methods: After due ethical approval, 30 animals were treated with 40mg/kg single dose of 7,12-dimethylbenzene anthracene (DMBA) as a model for DNA damage and induction of carcinogenesis. Five animals each received normal saline (normal), low dose artemisinin (Art; 4mg/kg), low dose caffeine (Caff; 25mg/kg), low dose combination of caff + art (25+4mg/kg), high dose combination of caff + art (50+8mg/kg) or no treatment (DMBA). All treatment doses were orally administered daily for two weeks post DMBA treatment. Nitric oxide levels and p53 relative gene expression was carried out using primer-specific RT-PCR, GAPDH was used as loading control and amplicons were resolved by gel electrophoresis. Results: DMBA induced lesions in breast, liver, and lung tissues evident from histology analysis, compared to normal group. In all 3 tissues, caffeine (25mg/kg) and combination of caff + art (25+4mg/kg) significantly reduced p53 gene expression (p < 0.05), but there was significant increase in the group treated with low dose art (4mg/kg) and high dose caff + art, which were similar to DMBA group (p<0.05). In lungs, nitric oxide (NO) increased in all groups but not in caffeine, in the liver NO decreased with caffeine or its combination with art, compared to DMBA group. Conclusions: This study shows a dose-dependent synergistic anticancer effects of caffeine and artemisinin combination on p53 gene and nitric oxide regulation hence can mitigate tumor development.
Dokunmu, T. M , Opara, S. C , Imaga, N. Awa , Awani, O. U , Enoma, D. O and Adelani, B. I (2023). P53 Gene Expression and Nitric Oxide Levels after Artemisinin-Caffeine Treatment in Breast, Lungs and Liver of DMBA-Induced Tumorigenesis. Asian Pacific Journal of Cancer Prevention, 24(2), 451-458. doi: 10.31557/APJCP.2023.24.2.451
MLA
Dokunmu, T. M, , Opara, S. C, , Imaga, N. Awa, , Awani, O. U, , Enoma, D. O, and Adelani, B. I. "P53 Gene Expression and Nitric Oxide Levels after Artemisinin-Caffeine Treatment in Breast, Lungs and Liver of DMBA-Induced Tumorigenesis", Asian Pacific Journal of Cancer Prevention, 24, 2, 2023, 451-458. doi: 10.31557/APJCP.2023.24.2.451
HARVARD
Dokunmu, T. M, Opara, S. C, Imaga, N. Awa, Awani, O. U, Enoma, D. O, Adelani, B. I (2023). 'P53 Gene Expression and Nitric Oxide Levels after Artemisinin-Caffeine Treatment in Breast, Lungs and Liver of DMBA-Induced Tumorigenesis', Asian Pacific Journal of Cancer Prevention, 24(2), pp. 451-458. doi: 10.31557/APJCP.2023.24.2.451
CHICAGO
T. M Dokunmu , S. C Opara , N. Awa Imaga , O. U Awani , D. O Enoma and B. I Adelani, "P53 Gene Expression and Nitric Oxide Levels after Artemisinin-Caffeine Treatment in Breast, Lungs and Liver of DMBA-Induced Tumorigenesis," Asian Pacific Journal of Cancer Prevention, 24 2 (2023): 451-458, doi: 10.31557/APJCP.2023.24.2.451
VANCOUVER
Dokunmu, T. M, Opara, S. C, Imaga, N. Awa, Awani, O. U, Enoma, D. O, Adelani, B. I P53 Gene Expression and Nitric Oxide Levels after Artemisinin-Caffeine Treatment in Breast, Lungs and Liver of DMBA-Induced Tumorigenesis. Asian Pacific Journal of Cancer Prevention, 2023; 24(2): 451-458. doi: 10.31557/APJCP.2023.24.2.451
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