In:
BioMed Research International, Hindawi Limited, Vol. 2018 ( 2018-09-27), p. 1-11
Kurzfassung:
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- κ B (NF- κ B) and reduced the phosphorylation of I κ B α and IKK α , suggesting the blockade of NF- κ B signaling. NF- κ B 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- κ B 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- κ B and ERK pathways, suggesting α -hederin as a promising candidate for intervention of colon cancer.
Materialart:
Online-Ressource
ISSN:
2314-6133
,
2314-6141
DOI:
10.1155/2018/2548378
Sprache:
Englisch
Verlag:
Hindawi Limited
Publikationsdatum:
2018
ZDB Id:
2698540-8
