Abstract
Background
The notion of cancer therapy is intrinsically subjected to multiple challenges due to the drug resistance and drug toxicity for normal tissues. Herniarin (7-methoxycoumarin) belongs to the naturally occurring aromatic phytochemicals and coumarins. Considering the boosting effect of nanocarriers in drug delivery, we investigated the proapoptotic, anti-metastatic properties, and molecular mechanism of herniarin-loaded solid lipid nanoparticles on human gastric adenocarcinoma (AGS), human colon adenocarcinoma (HT-29), human pancreatic carcinoma (Panc-1), and normal human skin fibroblast (HFF) cell lines.
Methods and results
The cytotoxicity of synthesized nanoparticle have been tested using MTT assay. The obtained results manifested that concentration of herniarin that exerts 50% cell growth inhibition (IC50) against HT-29, AGS, and Panc-1 was calculated 138.34, 123.46, and 83.744 µL, respectively. Given that nanoparticles showed lowest IC50 values on Panc-1 cell line, these cells were selected for further analysis. The apoptosis induction and cell cycle arrest were examined performing real-time PCR, flow cytometry, and DAPI/acridine orange-propidium iodide staining. The expression of apoptosis-related genes, including BCL-2, was decreased, while the expression of CASP9, CASP8, and CASP3 was increased in response to the treatment. Moreover, the expression of metastasis-related gene (MMP2) was significantly suppressed under Her-SLN-NPs treatment. According to the flow cytometry findings, we observed no cell cycle arrest at any stage.
Conclusion
Our funding manifested herniarin encapsulated solid lipid nanoparticles has potent therapeutic target against Panc-1 cell line.
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Data availability
The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.
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The authors are grateful to the Islamic Azad University of Mashhad for the laboratory facilities.
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Delkhah, A., Karimi, E. & Farivar, S. Herniarin-loaded solid lipid nanoparticles: promising molecular mechanism and therapeutic potential against pancreatic cancer line. Mol Biol Rep 50, 6469–6479 (2023). https://doi.org/10.1007/s11033-023-08560-9
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DOI: https://doi.org/10.1007/s11033-023-08560-9