| Summary: | Magnetic iron oxide nanoparticles are among the most useful metal nanoparticles in biomedical applications. A previous study had confirmed that phytic acid-chitosan-iron oxide nanocomposite (Phy-CS-MNP) exhibited antiproliferative activity towards human colorectal cancer (HT-29) cells. Hence, in this work, we explored the in vitro cytotoxicity activity and mechanistic action of Phy-CS-MNP nanocomposite in modulating gene and protein expression profiles in HT-29 cell lines. Cell cycle arrest and apoptosis were evaluated by NovoCyte Flow Cytometer. The mRNA changes (cyclin-dependent kinase 4 (<i>Cdk4</i>), vascular endothelial growth factor A (<i>VEGFA</i>), c-Jun N-terminal kinase 1 (<i>JNK1</i>), inducible nitric oxide synthase (<i>iNOS</i>), and matrix metallopeptidase 9 (<i>MMP9</i>)) and protein expression (nuclear factor-kappa B (<i>NF-κB</i>) and cytochrome c) were assessed by quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. The data from our study demonstrated that treatment with Phy-CS-MNP nanocomposite triggered apoptosis and G<sub>0</sub>/G<sub>1</sub> cell cycle arrest. The transcriptional activity of <i>JNK1</i> and <i>iNOS</i> was upregulated after treatment with 90 μg/mL Phy-CS-MNP nanocomposite. Our results suggested that Phy-CS-MNP nanocomposite induced apoptosis and cell cycle arrest via an intrinsic mitochondrial pathway through modulation of Bax and Bcl-2 and the release of cytochrome c from the mitochondria into the cytosol.
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