Multiple Signal Pathways Involved in Crocetin-Induced Apoptosis in KYSE-150 Cells.

Pharmacology 2019 15;103(5-6):263-272. Epub 2019 Feb 15.

Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China,

Background: Crocetin is a carotenoid extracted from the traditional Chinese medical herb saffron. Previous studies have demonstrated that crocetin possesses anticancer properties that are effective against various cancers. As an extension of our earlier study, the present study explored the underlying mechanisms in crocetin's anticancer effect on KYSE-150 cells. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), Mitogen-activated protein kinases (MAPK), and p53/p21 signal pathways play an important role in carcinogenesis, progression, and metastasis of carcinoma cells. Thus, we investigated crocetin's effects on the PI3K/AKT, MAPK, and p53/p21 pathways in esophageal squamous carcinoma cell line KYSE-150 cells.

Methods: KYSE-150 cells were treated with various concentrations of crocetin. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltertrazolium bromide assay, Annexin V/PI stain as well as Rh123 stain were used to evaluate the cell viability, apoptosis, and MMP. Western blot was used to detect the expression of PI3K, AKT, ERK1/2, p38, c-Jun NH-terminal kinase (JNK), P53, P21, Bcl-2, Bax, and cleaved caspase-3, which were associated with cell proliferation and apoptosis.

Results: Our results showed that crocetin significantly inhibited the proliferation of KYSE-150 cells in a dose- and time-dependent manner. Crocetin also markedly induced cell apoptosis. Furthermore, we have found that crocetin not only inhibited the activation of PI3K/AKT, extracellular signal-regulated kinase-1/2 (ERK1/2), and p38 but also upregulated the p53/p21 level. These regulations ultimately triggered the mitochondrial-mediated apoptosis pathway with an eventual disruption of MMP, increased levels of Bax and cleaved caspase-3, and decreased levels of Bcl-2.

Conclusions: These findings suggested that crocetin interfered with multiple signal pathways in KYSE-150 cells. Therefore, this study suggested that crocetin could potentially be used as a therapeutic candidate for the treatment of esophageal cancer.

Download full-text PDF

Source
http://dx.doi.org/10.1159/000487956DOI Listing
April 2019
3 Reads

Publication Analysis

Top Keywords

kyse-150 cells
20
signal pathways
12
mapk p53/p21
8
crocetin
8
crocetin inhibited
8
bax cleaved
8
suggested crocetin
8
erk1/2 p38
8
cleaved caspase-3
8
multiple signal
8
cells
6
kyse-150
6
metastasis carcinoma
4
regulations ultimately
4
5-diphenyltertrazolium bromide
4
bromide assay
4
ultimately triggered
4
crocetin 3-4
4
3-4 5-dimethylthiazol-2-yl-2
4
assay annexin
4

Similar Publications