Chitosan-loaded piperlongumine nanoparticles and kaempferol enhance the anti-cancer action of doxorubicin in targeting of Ehrlich solid adenocarcinoma: in vivo and in silico modeling study

Chitosan-loaded piperlongumine nanoparticles and kaempferol enhance the anti-cancer action of doxorubicin in targeting of Ehrlich solid adenocarcinoma: in vivo and in silico modeling study

Doxorubicin is a chemotherapeutic drug that generates free radical-induced toxicities. Natural agents are used to potentiate or ameliorate the toxicity of chemotherapy. None of the studies investigating whether antioxidants or prooxidants should be used with chemotherapy have addressed their efficac...

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Bibliographic Details
Published in:Medical oncology (Northwood, London, England) Vol. 41; no. 2; p. 61
Main Authors: Ibrahim, Fawziya A. R., Hussein, Neveen A., Soliman, Aisha Y. M., shalaby, Thanaa I., Rashad, Mona M., Matar, Noura A., El-Sewedy, Tarek S.
Format: Journal Article
Language:English
Published: New York Springer US 23-01-2024
Springer Nature B.V
Subjects:
Adenocarcinoma
Animals
Antioxidants
Benzodioxoles
Cancer
Chemotherapy
Chitosan
Computer Simulation
Doxorubicin - pharmacology
Hematology
Internal Medicine
Kaempferols - pharmacology
Medicine
Medicine & Public Health
Mice
Molecular Docking Simulation
Nanoparticles
Oncology
Original Paper
Pathology
Tumors
Piperlongumine
In silico
Chitosan nanoparticles
Kaempferol
Doxorubicin
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Summary:Doxorubicin is a chemotherapeutic drug that generates free radical-induced toxicities. Natural agents are used to potentiate or ameliorate the toxicity of chemotherapy. None of the studies investigating whether antioxidants or prooxidants should be used with chemotherapy have addressed their efficacy in the same study. Therefore, the aim of this study was to investigate the potential synergy between doxorubicin and two natural rarely in vivo studied anticancer agents; the antioxidant “Kaempferol” and prooxidant “Piperlongumine” in Ehrlich tumor mice model. 77 albino mice were divided into 11 groups; Ehrlich ascites carcinoma cells were injected intramuscularly to develop solid tumors. After 14 days, intratumoral injections of single or combinations of free or Chitosan nanoparticles loaded with doxorubicin, Piperlongumine, and Kaempferol were performed. Tumor Characterization of nanoparticles was measured, tumors were histopathologically examined and evaluation of expression for cancer-related genes by real-time PCR. In silico molecular docking was performed to uncover potential novel targets for Piperlongumine and Kaempferol. Despite receiving half of the overall dose compared to the free drugs, the combined doxorubicin/ piperlongumine-chitosan nanoparticles treatment was the most efficient in reducing tumor volume; down-regulating Cyclin D1 , and BCL2; as well as the Beclin-1, and Cyclophilin A genes modulating growth, apoptosis, autophagy, and metastasis, respectively; up-regulating the Glutathione peroxidase expression as a defense mechanism protecting from oxidative damage. When combined with doxorubicin, Kaempferol and Piperlongumine were effective against Ehrlich solid tumors. However, the combination with the Piperlongumine-loaded chitosan nanoparticles significantly enhanced its anticancer effect compared to the Kaempferol or the same free compounds.
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ISSN:1559-131X
1357-0560
1559-131X
DOI:10.1007/s12032-023-02282-5