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
Abstract
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;…
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