Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C
Abstract 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 o...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10644-5 |
| _version_ | 1797864412063727616 |
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| author | Rana R. El Sadda Zahraa R. Elshahawy Entsar A. Saad |
| author_facet | Rana R. El Sadda Zahraa R. Elshahawy Entsar A. Saad |
| author_sort | Rana R. El Sadda |
| collection | DOAJ |
| description | Abstract 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 IC50 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 IC50 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. |
| first_indexed | 2024-04-09T22:52:37Z |
| format | Article |
| id | doaj.art-34b41baf062b4eb4b48bb57e13b979ff |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T22:52:37Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-34b41baf062b4eb4b48bb57e13b979ff2023-03-22T11:34:13ZengBMCBMC Cancer1471-24072023-02-0123111010.1186/s12885-023-10644-5Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin CRana R. El Sadda0Zahraa R. Elshahawy1Entsar A. Saad2Chemistry Department, Faculty of Science, Damietta UniversityChemistry Department, Faculty of Science, Damietta UniversityChemistry Department, Faculty of Science, Damietta UniversityAbstract 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 IC50 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 IC50 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.https://doi.org/10.1186/s12885-023-10644-5CaspaseSynergisticCA19.9AFPBAXp53 |
| spellingShingle | Rana R. El Sadda Zahraa R. Elshahawy Entsar A. Saad Biochemical and pathophysiological improvements in rats with thioacetamide induced-hepatocellular carcinoma using aspirin plus vitamin C BMC Cancer Caspase Synergistic CA19.9 AFP BAX p53 |
| 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 | Caspase Synergistic CA19.9 AFP BAX p53 |
| url | https://doi.org/10.1186/s12885-023-10644-5 |
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