Novel antitumor activity of the combined treatment of galloylquinic acid compounds with doxorubicin in solid Ehrlich carcinoma model via the Notch signaling pathway modulation

The solid tumor model was induced by subcutaneous inoculation of Ehrlich carcinoma cells in the right hind limb of mice, after serial syngeneic cell passages in the peritoneal cavity. Sixty mice were allocated into five groups including treated groups with galloylquinic acid compounds, doxorubicin,...

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Bibliographic Details
Published in:Life sciences (1973) 2022-06, Vol.299, p.1
Main Authors: El-Salam, Mohamed A Abd, El-Tanbouly, Ghada S, Bastos, Jairo K, Metwaly, Heba A
Format: Article
Language:English
Subjects:
Acids
Anticancer properties
Antitumor activity
Cancer
Caspase-3
Cell death
Chemotherapy
Combined treatment
Cyclin D1
Doxorubicin
Inoculation
Interleukin 6
NF-κB protein
Notch1 protein
Oxidative stress
Side effects
Signal transduction
Signaling
Solid tumors
Tissues
Tumor necrosis factor-α
Tumors
Vascular endothelial growth factor
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Summary:The solid tumor model was induced by subcutaneous inoculation of Ehrlich carcinoma cells in the right hind limb of mice, after serial syngeneic cell passages in the peritoneal cavity. Sixty mice were allocated into five groups including treated groups with galloylquinic acid compounds, doxorubicin, and their combination. Normal and tumor control groups were also assigned. Tissue homogenates were collected to measure the levels of the Notch-1, Hes-1, Jagged-1, TNF-α, IL-6 and VEGF, as well as SOD, MDA, and GSH. Histopathological and immunohistochemical examinations of tumor or control tissues were also performed for the levels of NF-κB p65, cyclin D1 and caspase 3 activity. Key findings Our results showed that the combined treatment of galloylquinic acid compounds with doxorubicin significantly decreased the levels of the Notch-1, Hes-1, Jagged-1, TNF-α, IL-6, VEGF, NF-κB p65, and cyclin D1 in tumor tissues. Moreover, the compounds induced cancer cell death as evidence by increasing the caspase 3 activity, and they possessed potent inhibitory effects on oxidative stress. Significance Galloylquinic acid compounds exhibited promising antineoplastic effects and promoted the chemosensitivity of doxorubicin, mainly by modulating the Notch signaling pathway and its downstream effectors. These compounds may be considered in solid tumors treatment for improving the efficacy and reducing the side effects of chemotherapeutic agents.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.]fs.2022.120497