Elucidation of the Chemopreventive Role of Stigmasterol Against Jab1 in Gall Bladder Carcinoma.
Apoptosis
/ drug effects
COP9 Signalosome Complex
/ genetics
Carcinoma
/ genetics
Cell Proliferation
/ drug effects
Cell Transformation, Neoplastic
/ drug effects
Chemoprevention
/ methods
Gallbladder Neoplasms
/ genetics
HEK293 Cells
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Peptide Hydrolases
/ genetics
Primary Cell Culture
Signal Transduction
/ drug effects
Stigmasterol
/ pharmacology
Tumor Cells, Cultured
Jab1 gene
Stigmasterol
apoptosis
caspase-3
gall bladder cancer
therapeutics.
Journal
Endocrine, metabolic & immune disorders drug targets
ISSN: 2212-3873
Titre abrégé: Endocr Metab Immune Disord Drug Targets
Pays: United Arab Emirates
ID NLM: 101269157
Informations de publication
Date de publication:
2019
2019
Historique:
received:
03
08
2018
revised:
06
11
2018
accepted:
19
01
2019
pubmed:
8
2
2019
medline:
13
2
2020
entrez:
8
2
2019
Statut:
ppublish
Résumé
Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet. In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells. In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells. Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis. Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.
Sections du résumé
BACKGROUND
Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet.
OBJECTIVE
In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells.
METHODS
In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells.
RESULTS
Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis.
CONCLUSION
Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.
Identifiants
pubmed: 30727937
pii: EMIDDT-EPUB-96387
doi: 10.2174/1871530319666190206124120
doi:
Substances chimiques
Intracellular Signaling Peptides and Proteins
0
Stigmasterol
99WUK5D0Y8
Peptide Hydrolases
EC 3.4.-
COPS5 protein, human
EC 3.4.-.-
COP9 Signalosome Complex
EC 3.4.19.12
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
826-837Informations de copyright
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