Autor: |
Chandrababu, Gopika, Varkey, Merlin, Devan, Aswathy R., Anjaly, M. V., Unni, Ashok R., Nath, Lekshmi R. |
Předmět: |
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Zdroj: |
Naunyn-Schmiedeberg's Archives of Pharmacology; Oct2023, Vol. 396 Issue 10, p2461-2467, 7p |
Abstrakt: |
Context : Phytochemicals have been promising candidates for cancer therapy, affecting various cancer initiation and progression stages. Kaempferide is a mono methoxy flavone that shows potent anticancer effects on multiple cancers both in vitro and in vivo. Materials and methods: We evaluated the anticancer activity of kaempferide against HCC using an MTT ((3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. HepG2, Huh7, and N1S1 were used for preliminary in vitro studies. This is followed by an apoptosis analysis assessed by caspase-3 and 9. The in vivo effects of the compound were studied in the N1S1 orthotopically injected SD (Sprague Dawley) rat model, where the animal was given kaempferide (25 mg/kg thrice a week) and vehicle (Cremophor:ethanol) iv. The expression of caspase-9 and a critical tumor marker, transforming growth factor beta 1 (TGF-β 1), were assessed in both control and treatment tumor samples. Results: Kaempferide-induced dose-dependent cytotoxicity in three HCC cell lines (HepG2: IC50 = 27.94 ± 2.199 µM; Huh7: IC50 = 25.65 ± 0.956 µM; and N1S1: IC50 = 15.18 ± 3.68 µM). Furthermore, caspase-dependent apoptosis was confirmed in vitro. Kaempferide showed a significant reduction in tumor size and tumor volume in vivo. Histopathological evaluation by hematoxylin and eosin (H&E) staining confirmed that altered cells were significantly demolished in the kaempferide-treated animals, which correlates with tumor reduction compared to the vehicle-treated group. Caspase-9 levels were also found to be increased in the treatment group. TGF-β 1, a crucial marker in invasion and metastasis of liver cancer, was also downregulated in the treatment group (control = 207.8 ± 22.9 pg/mL and kaempferide-treated = 157.3 ± 13.8 pg/mL). Conclusion: We report for the first time the potential of kaempferide as a promising alternative against HCC, which further warrants its clinical validation. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
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