The HIV reverse transcriptase Inhibitor Tenofovir suppressed DMH/HFD‐induced colorectal cancer in Wistar rats

Abstract

Colon rectal cancer (CRC) is the second commonest malignancy in developed countries and a significant cause of mortality. Tenofovir reportedly reduces the risk of hepatocellular carcinoma and interferes with cell cycle and cell proliferation. The current study investigated the potential antitumor effect of tenofovir against experimentally induced CRC. CRC was induced by 1,2-dimethylhydrazine (DMH, 20 mg/kg, once a week) and high-fat diet (HFD) in Wistar rats. Rats received tenofovir at a dose of 25 or 50 mg/kg (i.p.) for 24 weeks. Tenofovir-25 failed to significantly decrease the total number of dysplasia, adenoma and adenocarcinoma and to improve histopathological changes; however, tenofovir-50 resulted in no tumors seen in the colon lumen and a significant decrease in the total number of dysplasia and no adenoma or adenocarcinoma observed compared to DMH/HFD group. Tenofovir-25 failed to attenuate DMH/HFD-induced cell proliferation, whereas tenofovir-50 significantly decreased cell proliferation revealed by the decreased PCNA expression. Tenofovir-25 also failed to attenuate DMH/HFD-induced oxidative stress, whereas tenofovir-50 significantly attenuated oxidative stress as indicated by the decreased MDA concentration and SOD activity along with the increased GSH concentrations. Moreover, tenofovir-50 decreased Bcl-2 and cyclin D1 expressions in colon tissues compared with DMH/HFD group.Tenofovir-50 also significantly decreased INF-ɤ concentration in colon tissues. These findings suggest that the high dose of tenofovir (50 mg/kg) has antitumor potential against DMH/HFD-induced CRC, which might be mediated through the inhibition of cell proliferation, oxidative stress, and inflammation.

The Potential Chemopreventive Effect of Andrographis paniculata on 1,2-Dimethylhydrazine and High-Fat-Diet-Induced Colorectal Cancer in Sprague Dawley Rats

“…A high-fat diet can lead to obesity, which causes the adipocyte to release more adipokines that cause inflammation [ 20 ]. In this study, the histopathological examination of DMH/HFD rats demonstrated abnormal development in the colon tissue matching with previous findings [ 37 ]. Furthermore, DMH-induced rats with a high-fat diet had a considerably greater number of ACF than DMH-induced rats with a normal-fat diet.…”

“…The specimen slides were stained with hematoxylin and eosin. The stained specimen slides were covered using slip slides [ 37 ]. The histopathology changes were examined by a pathologist.…”

The role of gut microbiota and drug interactions in the development of colorectal cancer

“…Therefore, it can produce an anti-CRC effect by interfering with the virus. Zidovudine is a nucleoside antiretroviral drug inhibiting CRC cell proliferation ( Fang et al, 2017 ; Sherif et al, 2021 ). Ganciclovir inhibits the NLR family pyrin domain containing 3 activations and reduces the irinotecan-induced intestinal toxicity ( Huang et al, 2020 ).…”

Overcoming Therapy Resistance in Colon Cancer by Drug Repurposing

“…Tenofovir also inhibits the activity of human telomerase [119], a crucial enzyme for tumorigenesis and cancer proliferation, whose inhibition represents a promising therapeutic strategy in cancer treatment [120,121]. Sherif et al demonstrated that rats receiving tenofovir at a dose of 50 mg/kg for 24 weeks had diminished colorectal cell proliferation attributed to decreased Bcl-2 and cyclin D1 expression [60]. Zidovudine, also known as azidothymidine, is another nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of human immunodeficiency virus (HIV) [122].…”