An Intrinsic Mitochondrial Pathway Is Required for Phytic Acid-Chitosan-Iron Oxide Nanocomposite (Phy-CS-MNP) to Induce G<sub>0</sub>/G<sub>1</sub> Cell Cycle Arrest and Apoptosis in the Human Colorectal Cancer (HT-29) Cell Line
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 thi...
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MDPI AG
2018-10-01
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| Online Access: | https://www.mdpi.com/1999-4923/10/4/198 |
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| author | Bee Ling Tan Mohd Esa Norhaizan Lee Chin Chan |
| author_facet | Bee Ling Tan Mohd Esa Norhaizan Lee Chin Chan |
| author_sort | Bee Ling Tan |
| collection | DOAJ |
| description | 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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| language | English |
| last_indexed | 2024-12-10T08:17:40Z |
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| spelling | doaj.art-32e223617852431394c77862c78d8d452022-12-22T01:56:25ZengMDPI AGPharmaceutics1999-49232018-10-0110419810.3390/pharmaceutics10040198pharmaceutics10040198An Intrinsic Mitochondrial Pathway Is Required for Phytic Acid-Chitosan-Iron Oxide Nanocomposite (Phy-CS-MNP) to Induce G<sub>0</sub>/G<sub>1</sub> Cell Cycle Arrest and Apoptosis in the Human Colorectal Cancer (HT-29) Cell LineBee Ling Tan0Mohd Esa Norhaizan1Lee Chin Chan2Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, MalaysiaDepartment of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, MalaysiaDepartment of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, MalaysiaMagnetic 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.https://www.mdpi.com/1999-4923/10/4/198c-Jun N-terminal kinase 1cytochrome ccytotoxicityinducible nitric oxide synthase |
| spellingShingle | Bee Ling Tan Mohd Esa Norhaizan Lee Chin Chan An Intrinsic Mitochondrial Pathway Is Required for Phytic Acid-Chitosan-Iron Oxide Nanocomposite (Phy-CS-MNP) to Induce G<sub>0</sub>/G<sub>1</sub> Cell Cycle Arrest and Apoptosis in the Human Colorectal Cancer (HT-29) Cell Line Pharmaceutics c-Jun N-terminal kinase 1 cytochrome c cytotoxicity inducible nitric oxide synthase |
| title | An Intrinsic Mitochondrial Pathway Is Required for Phytic Acid-Chitosan-Iron Oxide Nanocomposite (Phy-CS-MNP) to Induce G<sub>0</sub>/G<sub>1</sub> Cell Cycle Arrest and Apoptosis in the Human Colorectal Cancer (HT-29) Cell Line |
| title_full | An Intrinsic Mitochondrial Pathway Is Required for Phytic Acid-Chitosan-Iron Oxide Nanocomposite (Phy-CS-MNP) to Induce G<sub>0</sub>/G<sub>1</sub> Cell Cycle Arrest and Apoptosis in the Human Colorectal Cancer (HT-29) Cell Line |
| title_fullStr | An Intrinsic Mitochondrial Pathway Is Required for Phytic Acid-Chitosan-Iron Oxide Nanocomposite (Phy-CS-MNP) to Induce G<sub>0</sub>/G<sub>1</sub> Cell Cycle Arrest and Apoptosis in the Human Colorectal Cancer (HT-29) Cell Line |
| title_full_unstemmed | An Intrinsic Mitochondrial Pathway Is Required for Phytic Acid-Chitosan-Iron Oxide Nanocomposite (Phy-CS-MNP) to Induce G<sub>0</sub>/G<sub>1</sub> Cell Cycle Arrest and Apoptosis in the Human Colorectal Cancer (HT-29) Cell Line |
| title_short | An Intrinsic Mitochondrial Pathway Is Required for Phytic Acid-Chitosan-Iron Oxide Nanocomposite (Phy-CS-MNP) to Induce G<sub>0</sub>/G<sub>1</sub> Cell Cycle Arrest and Apoptosis in the Human Colorectal Cancer (HT-29) Cell Line |
| title_sort | intrinsic mitochondrial pathway is required for phytic acid chitosan iron oxide nanocomposite phy cs mnp to induce g sub 0 sub g sub 1 sub cell cycle arrest and apoptosis in the human colorectal cancer ht 29 cell line |
| topic | c-Jun N-terminal kinase 1 cytochrome c cytotoxicity inducible nitric oxide synthase |
| url | https://www.mdpi.com/1999-4923/10/4/198 |
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