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Anti-proliferative activity of chitosan-coated oxypeucedanin nano-chitosomes (COPD-NCs) against human HT-29 colon cancer cells: in vitro study

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Abstract

Oxypeucedanin (OPD) as a powerful anti-proliferative agent found in the Angelicae dahuricae has been used to suppress cancer cell growth. However, the hydrophobic chemical structure has limited its solubility and bio-accessibility. This is the first time OPD is encapsulated into a nano-liposomal structure and coated with poly-cationic chitosan polymer as the oxypeucedanin drug delivery system to evaluate its antioxidant and anti-colon cancer potential. The chitosan-coated oxypeucedanin nano-chitosomes (COPD-NCs) were synthesized utilizing the thin-layer hydration method and characterized by FESEM, DLS, FTIR, and zeta potential analysis. The anti-cancer potential of COPD-NC was analyzed by measuring the cell survival rate (MTT assay) and studying the cellular death type (AO/PI staining) following the increased treatment concentrations of COPD-NC on the HT-29 colon cancer cell line. Moreover, the COPD-NCs’ apoptotic activity was verified by analyzing Cas-3 and Cas-9 gene expression profiles. Finally, the COPD-NCs’ antioxidant activity was evaluated by applying ABTS, DPPH, and FRAP antioxidant assays. The 258.26-nm COPD-NCs significantly inhibited the HT-29 colon cancer cells compared with the normal fibroblast HFF cells. The up-regulated Cas-3 and Cas-9 gene expression exhibited the COPD-NCs’ apoptotic activity. Also, the COPD-NCs’ apoptotic activity was verified by detecting the increased apoptotic bodies following the AO/PI fluorescent staining in the increased exposure doses of COPD-NCs. Ultimately, the COPD-NCs meaningfully inhibited the ABTS-DPPH radicals and exhibited an appropriate FRAP-reductive potential. The designed nanostructure for COPD-NCs significantly improved its antioxidant potential and selective cytotoxicity on human HT-29 human cancer cells, which makes them a safe selective natural drug delivery system. Therefore, the COPD-NCs can selectively induce apoptotic death in human HT-29 cancer cells and have the potential to be studied as an anti-colon cancer compound. However, further cancer and normal cell lines are required to verify their selective cytotoxicity.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by the Islamic Azad University, Tehran, Iran, and therefore is appreciated by the author.

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This research was performed at personal expense in the laboratory of Islamic Azad University of Tehran.

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Muntadher Aqeel Obaid Almohammed, Mahshid Sharbatiyan and Hasti Nasiraei Haghighi: Methodology, Investigation, Formal analysis, Software and Writing-Original draft. Sakineh Meshkani, Masoud Homayouni Tabrizi: Supervision, Data curation, Conceptualization, Validation and Writing- Reviewing. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Sakineh Meshkani.

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Almohammed, M.A.O., Meshkani, S., Homayouni Tabrizi, M. et al. Anti-proliferative activity of chitosan-coated oxypeucedanin nano-chitosomes (COPD-NCs) against human HT-29 colon cancer cells: in vitro study. Naunyn-Schmiedeberg's Arch Pharmacol 397, 2133–2143 (2024). https://doi.org/10.1007/s00210-023-02748-3

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