α -Hederin Arrests Cell Cycle at G2/M Checkpoint and Promotes Mitochondrial Apoptosis by Blocking Nuclear Factor-κB Signaling in Colon Cancer Cells.
Colon cancer represents the third most common malignancy worldwide. New drugs with high efficaciousness and safety for the treatment of colon cancer are urgently needed in clinical context. Here, we were aimed to evaluate the antitumor activity of the natural compound α-hederin in human colon cancer...
| Publicado en: | BioMed Research International Vol. 2018; pp. 1 - 12 |
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| Autores principales: | , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
9/27/2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=132009683&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 132009683 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 9/27/2018 vid: 2018 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 132009683 132009683 132009683 10.1155/2018/2548378 132009683 ppf: 1 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: α -Hederin Arrests Cell Cycle at G2/M Checkpoint and Promotes Mitochondrial Apoptosis by Blocking Nuclear Factor-κB Signaling in Colon Cancer Cells. aug: au: Sun, Dongdong Shen, Weixing Zhang, Feng Fan, Huisen Tan, Jiani Li, Liu Xu, Changliang Zhang, Haibin Yang, Ye Cheng, Haibo affil: The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China sug: subj: Steroids Pharmacodynamics Cell Cycle Drug Effects Mitochondria Drug Effects Apoptosis Drug Effects NF-kappa B Drug Effects Signal Transduction Drug Effects Colonic Neoplasms Drug Therapy Cell Line, Tumor Drug Effects Human Interleukins Drug Effects In Vitro Studies Inflammation Cell Viability Drug Effects RNA, Messenger Drug Effects Gene Expression Drug Effects Growth Substances Drug Effects Biochemical Phenomena Drug Effects Hemeproteins Drug Effects Caspases Drug Effects Transferases Drug Effects Biological Transport Drug Effects Phosphorylation Drug Effects Chelating Agents ab: Colon cancer represents the third most common malignancy worldwide. New drugs with high efficaciousness and safety for the treatment of colon cancer are urgently needed in clinical context. Here, we were aimed to evaluate the antitumor activity of the natural compound α-hederin in human colon cancer cells. We treated SW620 cells with interleukin-6 (IL-6) in vitro to mimic the paracrine inflammatory microenvironment of tumor cells. α-Hederin concentration dependently reduced the viability of IL-6-stimulated SW620 cells. α-Hederin increased the number of IL-6-stimulated SW620 cells at the G2/M phase and reduced the mRNA and protein expression of cyclin B1 and CDK1. Moreover, α-hederin induced apoptosis and loss of mitochondrial membrane potential in IL-6-stimulated SW620 cells. α-Hederin downregulated Bcl-2 expression, upregulated Bax expression, and promoted cytochrome c release from mitochondria into cytoplasm. Additionally, α-hederin elevated the levels of cleaved-caspase-9, cleaved-caspase-3, and cleaved-PARP, but had little effects on the levels of cleaved-caspase-8. Moreover, α-hederin prevented the nuclear translocation of nuclear factor-κB (NF-κB) and reduced the phosphorylation of IκBα and IKKα, suggesting the blockade of NF-κB signaling. NF-κB inhibitor PDTC not only produced similar proapoptotic effects on IL-6-stimulated SW620 cells as α-hederin did, but also synergistically enhanced α-hederin’s proapoptotic effects. Furthermore, α-hederin inhibited the phosphorylation of ERK in IL-6-stimulated SW620 cells, which was involved in α-hederin blockade of NF-κB nuclear translocation. Altogether, α-hederin suppressed viability, induced G2/M cell cycle arrest, and stimulated mitochondrial and caspase-dependent apoptosis in colon cancer cells, which were associated with disruption of NF-κB and ERK pathways, suggesting α-hederin as a promising candidate for intervention of colon cancer. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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