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Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, so we should be concerned and look for effective/less-harmful treatments than chemotherapeutics already clinically in application. Aspirin works well ''in conjunction'' with other the...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942340/ https://www.ncbi.nlm.nih.gov/pubmed/36809998 http://dx.doi.org/10.1186/s12885-023-10644-5 |
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author | El Sadda, Rana R. Elshahawy, Zahraa R. Saad, Entsar A. |
author_facet | El Sadda, Rana R. Elshahawy, Zahraa R. Saad, Entsar A. |
author_sort | El Sadda, Rana R. |
collection | PubMed |
description | BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, so we should be concerned and look for effective/less-harmful treatments than chemotherapeutics already clinically in application. Aspirin works well ''in conjunction'' with other therapies for HCC since aspirin can boost the sensitivity of anti-cancer activity. Vitamin C also was shown to have antitumor effects. In this study, we examined the anti-HCC activities of synergistic combination (aspirin and vitamin C) vs. doxorubicin on HCC-bearing rats and hepatocellular carcinoma (HepG-2) cells. METHODS: In vitro, we evaluated IC(50) and selectivity index (SI) using HepG-2 and human lung fibroblast (WI-38) cell lines. In vivo, four rat groups were used: Normal, HCC (intraperitoneally (i.p.) administered 200 mg thioacetamide/kg/twice a week), HCC + DOXO (HCC-bearing rats i.p. administered 0.72 mg doxorubicin (DOXO)/rat/once a week), and HCC + Aspirin + Vit. C (i.p. administered vitamin C (Vit. C) 4 g/kg/day after day concomitant with aspirin 60 mg/kg/orally day after day). We evaluated biochemical factors [aminotransferases (ALT and AST), albumin, and bilirubin (TBIL) spectrophotometrically, caspase 8 (CASP8), p53, Bcl2 associated X protein (BAX), caspase 3 (CASP3), alpha-fetoprotein (AFP), cancer antigen 19.9 (CA19.9), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) using ELISA], and liver histopathologically. RESULTS: HCC induction was accompanied by significant time-dependent elevations in all measured biochemical parameters except the p53 level significantly declined. Liver tissue architecture organization appeared disturbed with cellular infiltration, trabeculae, fibrosis, and neovascularization. Following drug medication, all biochemical levels significantly reversed toward normal, with fewer signs of carcinogenicity in liver tissues. Compared to doxorubicin, aspirin & vitamin C therapy ameliorations were more appreciated. In vitro, combination therapy (aspirin & vitamin C) exhibited potent cytotoxicity (HepG-2 IC(50) of 17.41 ± 1.4 µg/mL) and more excellent safety with a SI of 3.663. CONCLUSIONS: Based on our results, aspirin plus vitamin C can be considered reliable, accessible, and efficient synergistic anti-HCC medication. |
format | Online Article Text |
id | pubmed-9942340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-99423402023-02-22 Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C El Sadda, Rana R. Elshahawy, Zahraa R. Saad, Entsar A. BMC Cancer Research BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, so we should be concerned and look for effective/less-harmful treatments than chemotherapeutics already clinically in application. Aspirin works well ''in conjunction'' with other therapies for HCC since aspirin can boost the sensitivity of anti-cancer activity. Vitamin C also was shown to have antitumor effects. In this study, we examined the anti-HCC activities of synergistic combination (aspirin and vitamin C) vs. doxorubicin on HCC-bearing rats and hepatocellular carcinoma (HepG-2) cells. METHODS: In vitro, we evaluated IC(50) and selectivity index (SI) using HepG-2 and human lung fibroblast (WI-38) cell lines. In vivo, four rat groups were used: Normal, HCC (intraperitoneally (i.p.) administered 200 mg thioacetamide/kg/twice a week), HCC + DOXO (HCC-bearing rats i.p. administered 0.72 mg doxorubicin (DOXO)/rat/once a week), and HCC + Aspirin + Vit. C (i.p. administered vitamin C (Vit. C) 4 g/kg/day after day concomitant with aspirin 60 mg/kg/orally day after day). We evaluated biochemical factors [aminotransferases (ALT and AST), albumin, and bilirubin (TBIL) spectrophotometrically, caspase 8 (CASP8), p53, Bcl2 associated X protein (BAX), caspase 3 (CASP3), alpha-fetoprotein (AFP), cancer antigen 19.9 (CA19.9), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) using ELISA], and liver histopathologically. RESULTS: HCC induction was accompanied by significant time-dependent elevations in all measured biochemical parameters except the p53 level significantly declined. Liver tissue architecture organization appeared disturbed with cellular infiltration, trabeculae, fibrosis, and neovascularization. Following drug medication, all biochemical levels significantly reversed toward normal, with fewer signs of carcinogenicity in liver tissues. Compared to doxorubicin, aspirin & vitamin C therapy ameliorations were more appreciated. In vitro, combination therapy (aspirin & vitamin C) exhibited potent cytotoxicity (HepG-2 IC(50) of 17.41 ± 1.4 µg/mL) and more excellent safety with a SI of 3.663. CONCLUSIONS: Based on our results, aspirin plus vitamin C can be considered reliable, accessible, and efficient synergistic anti-HCC medication. BioMed Central 2023-02-21 /pmc/articles/PMC9942340/ /pubmed/36809998 http://dx.doi.org/10.1186/s12885-023-10644-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research El Sadda, Rana R. Elshahawy, Zahraa R. Saad, Entsar A. Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C |
title | Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C |
title_full | Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C |
title_fullStr | Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C |
title_full_unstemmed | Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C |
title_short | Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C |
title_sort | biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin c |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942340/ https://www.ncbi.nlm.nih.gov/pubmed/36809998 http://dx.doi.org/10.1186/s12885-023-10644-5 |
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