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.
Background: 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-cancer properties, although they are therapies for other diseases. When p53 is activated, it repairs DNA damage, prevents tumorigenesis and induces apoptosis whereas nitric oxide is a pro-apoptotic modulator which can upregulate p53 thereby reducing tumorigenesis. We evaluated the biochemical and p53 gene modulatory effects of doses of artemisinin-caffeine combination on breast, lung and liver tumors 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 low dose artemisinin (4mg/kg), low dose caffeine (25mg/kg), low dose combination of Art + Caff (4+25mg/kg), high dose combination of Art + Caff (8+50 mg/kg) or no treatment. All treatment doses were orally administered daily for two weeks post-DMBA treatment, normal control received saline. Nitric oxide levels were assessed and p53 relative gene expression was determined by 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 were evident from histology analysis, compared to untreated group. In all 3 tissues, low dose caffeine and combination of Art + Caff significantly reduced p53 gene expression (p < 0.05), but there was significant increase in of p53 expression in low dose Art and high dose Art + Caff groups, which were similar to DMBA group (p<0.05). There was also decrease in nitric oxide levels in treated groups compared to DMBA group. Conclusions: This study shows a dose-dependent anticancer effects of caffeine and artemisinin combination on p53 gene and nitric oxide regulation and hence can mitigate against tumorigenesis. Citation Format: Titilope M. Dokunmu, Sandra C. Opara, Omiete U. Awani. p53 gene expression and nitric oxide levels after artemisinin-caffeine treatment in breast, lungs and liver of DMBA-induced tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5850.
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