Guggulsterone induces apoptosis and inhibits lysosomal-dependent migration in human bladder cancer cells.
Animals
Antineoplastic Agents, Phytogenic
/ pharmacology
Apoptosis
/ drug effects
Autophagy
/ drug effects
Caspase 3
/ metabolism
Cell Cycle Checkpoints
/ drug effects
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Humans
Lysosomes
/ drug effects
Mice, Inbred BALB C
Pregnenediones
/ pharmacology
TOR Serine-Threonine Kinases
/ metabolism
Urinary Bladder Neoplasms
/ drug therapy
Xenograft Model Antitumor Assays
Apoptosis
Autophagy
Bladder cancer
Guggulsterone
Migration
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
02
01
2021
revised:
18
04
2021
accepted:
27
04
2021
pubmed:
28
5
2021
medline:
7
7
2021
entrez:
27
5
2021
Statut:
ppublish
Résumé
The survival rate and therapeutic options for patients with bladder cancer have improved little in recent decades. Guggulsterone (GS), a phytoestrogen, has been investigated as an anticancer drug in various malignancies. The present study aimed to evaluate the anticancer effects of E-isomer and Z-isomer GS in the human bladder cancer cell lines TSGH8301 (low-grade) and T24 (high-grade) and their underlying mechanisms. The cell survival effect of GS was investigated by the MTT and colony formation assays in bladder cancer cell lines. Flow cytometry was used to analyze the cell cycle and cell death. Migration ability was measured by wound healing and transwell assays. Protein expression was determined by Western blot after GS treatment. The potency of GS on subcutaneous TSGH8301 bladder tumors was evaluated using an in vivo imaging system. E-isomer GS reduced the survival rate of both low- and high-grade human bladder cancer cells. GS caused cell cycle arrest, accompanied by the decrease and increase in cyclin A and p21 levels, respectively. Additionally, caspase-dependent apoptosis was observed following GS treatment. Furthermore, GS treatment downregulated mTOR-Akt signaling and induced autophagy with p62 and LC3β-II expression. Moreover, the farnesoid X receptor was involved in GS-inhibited cell growth. In addition, GS reduced the migration ability with a decrease in integrin-focal adhesion kinase and myosin light chain. Interestingly, the suppression of GS-mediated migration was prevented by the lysosomal inhibitor ammonium chloride (NH The current findings suggest that GS treatment may serve as a potential anticancer therapy for different grades of urothelial carcinoma.
Sections du résumé
BACKGROUND
BACKGROUND
The survival rate and therapeutic options for patients with bladder cancer have improved little in recent decades. Guggulsterone (GS), a phytoestrogen, has been investigated as an anticancer drug in various malignancies.
PURPOSE
OBJECTIVE
The present study aimed to evaluate the anticancer effects of E-isomer and Z-isomer GS in the human bladder cancer cell lines TSGH8301 (low-grade) and T24 (high-grade) and their underlying mechanisms.
METHODS
METHODS
The cell survival effect of GS was investigated by the MTT and colony formation assays in bladder cancer cell lines. Flow cytometry was used to analyze the cell cycle and cell death. Migration ability was measured by wound healing and transwell assays. Protein expression was determined by Western blot after GS treatment. The potency of GS on subcutaneous TSGH8301 bladder tumors was evaluated using an in vivo imaging system.
RESULTS
RESULTS
E-isomer GS reduced the survival rate of both low- and high-grade human bladder cancer cells. GS caused cell cycle arrest, accompanied by the decrease and increase in cyclin A and p21 levels, respectively. Additionally, caspase-dependent apoptosis was observed following GS treatment. Furthermore, GS treatment downregulated mTOR-Akt signaling and induced autophagy with p62 and LC3β-II expression. Moreover, the farnesoid X receptor was involved in GS-inhibited cell growth. In addition, GS reduced the migration ability with a decrease in integrin-focal adhesion kinase and myosin light chain. Interestingly, the suppression of GS-mediated migration was prevented by the lysosomal inhibitor ammonium chloride (NH
CONCLUSIONS
CONCLUSIONS
The current findings suggest that GS treatment may serve as a potential anticancer therapy for different grades of urothelial carcinoma.
Identifiants
pubmed: 34044254
pii: S0944-7113(21)00129-X
doi: 10.1016/j.phymed.2021.153587
pii:
doi:
Substances chimiques
Antineoplastic Agents, Phytogenic
0
Pregnenediones
0
pregna-4,17-diene-3,16-dione
A4PW148END
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
CASP3 protein, human
EC 3.4.22.-
Caspase 3
EC 3.4.22.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153587Informations de copyright
Copyright © 2021. Published by Elsevier GmbH.