An Intrinsic Mitochondrial Pathway Is Required for Phytic Acid-Chitosan-Iron Oxide Nanocomposite (Phy-CS-MNP) to Induce G0/G1 Cell Cycle Arrest and Apoptosis in the Human Colorectal Cancer (HT-29) Cell Line

Autor: Bee Ling Tan, Mohd Esa Norhaizan, Lee Chin Chan
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Pharmaceutics, Vol 10, Iss 4, p 198 (2018)
Druh dokumentu: article
ISSN: 1999-4923
DOI: 10.3390/pharmaceutics10040198
Popis: 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 (Cdk4), vascular endothelial growth factor A (VEGFA), c-Jun N-terminal kinase 1 (JNK1), inducible nitric oxide synthase (iNOS), and matrix metallopeptidase 9 (MMP9)) and protein expression (nuclear factor-kappa B (NF-κB) 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 G0/G1 cell cycle arrest. The transcriptional activity of JNK1 and iNOS 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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