Abstract
Background
Among the flavonoids, Myricetin (MCN) has negligible side effects and anti-cancer properties. However, the therapeutic potential of MCN has been limited mainly by its low bioavailability. Nanocarriers improve the bioavailability and stability of flavonoids. The toxic effects of MCN loaded in solid lipid nanoparticles (MCN-SLNs) on the HT-29 human colorectal cancer cells were investigated in this study.
Methods and results
HT-29 cells were exposed to the 30 µmol MCN or MCN-SLNs for 24 h. Colony formation, cell viability, apoptosis, and expression of the Bax, Bcl-2, and AIF (apoptosis-inducing factor) have been investigated. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) generation were also measured. The MCN-SLNs with appropriate characteristics and a slow sustained MCN release until 48 h made. MCN-SLNs could diminish colony numbers and survival of the HT-29 cells. The apoptosis index of MCN-SLNs-treated cells significantly increased compared to the free MCN (p < 0.001). The expression of Bax and AIF were elevated (p < 0.01 and p < 0.001, respectively) while Bcl-2 expression was decreased in MCN-SLNs treatment (p < 0.05). Moreover, MCN-SLNs significantly enhanced the ROS formation and reduced MMP compared to the free MCN-treated cells (p < 0.01).
Conclusions
The SLN formulation of MCN can effectively induce colon cancer cell death by raising ROS formation and activating the apoptosis process.
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Data availability
The authors confirm that the data supporting the findings of this study are available in the supplemental file.
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Acknowledgements
This work has received a Grant from the Ahvaz Jundishapur University of Medical Sciences of Iran. We thank our colleagues from the Cellular and Molecular Research Center.
Funding
This work has received a Grant from the Ahvaz Jundishapur University of Medical Sciences of Iran (No: CMRC-9640).
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LK: supervised the study, statistical data analysis, and critical reviewing of the manuscript. HA: performed sampling, collection of data, experiments, and data analysis. AA: designing the study, searching the literature, and manuscript preparation. AS: performed sampling. MAK: designing the study and manuscript editing.
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This study was performed based on ethical principles approved by the Ethics Committee of Ahvaz Jundishapur University of Medical Sciences, Iran (No: IR.AJUMS.REC.1396.1120).
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Alidadi, H., Ashtari, A., Samimi, A. et al. Myricetin loaded in solid lipid nanoparticles induces apoptosis in the HT-29 colorectal cancer cells via mitochondrial dysfunction. Mol Biol Rep 49, 8537–8545 (2022). https://doi.org/10.1007/s11033-022-07683-9
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DOI: https://doi.org/10.1007/s11033-022-07683-9