Guggulsterone induces apoptosis and inhibits lysosomal-dependent migration in human bladder cancer cells
Ying Chen1, Hisao-Hsien Wang2, Hsin-Han Chang1
1Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
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:
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:
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:
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 (NH4Cl). GS also reduced TSGH8301 bladder cancer cell progression by increasing the level of p21, cleaved caspase 3, cleaved poly (ADP-ribose) polymerase (PARP), and LC3β-II in vivo.
Conclusions:
The current findings suggest that GS treatment may serve as a potential anticancer therapy for different grades of urothelial carcinoma.
Insights
Guggulsterone (GS) shows potential as an anticancer therapy for bladder cancer, reducing cell survival, migration, and tumor progression by inducing apoptosis and autophagy. This phytoestrogen may offer new treatment options for urothelial carcinoma.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Bladder cancer treatment options and survival rates have seen limited improvement in recent decades.
- Guggulsterone (GS), a phytoestrogen, is being explored for its potential anticancer properties across various malignancies.
Purpose of the Study:
- To investigate the anticancer effects of E-isomer and Z-isomer Guggulsterone (GS) on human bladder cancer cell lines (TSGH8301 and T24).
- To elucidate the underlying molecular mechanisms of GS's anticancer activity in bladder cancer.
Main Methods:
- Cell viability assessed via MTT and colony formation assays.
- Cell cycle, apoptosis, and migration analyzed using flow cytometry, wound healing, and transwell assays.
- Protein expression (mTOR-Akt signaling, autophagy markers, apoptosis markers) evaluated by Western blot; in vivo efficacy tested on subcutaneous tumors.
Main Results:
- E-isomer GS significantly reduced survival in both low- and high-grade bladder cancer cells.
- GS induced cell cycle arrest, caspase-dependent apoptosis, and inhibited cell migration.
- GS downregulated mTOR-Akt signaling, induced autophagy, and involved the farnesoid X receptor in growth inhibition.
- In vivo studies confirmed reduced tumor progression with increased p21, cleaved caspase 3, PARP, and LC3β-II levels.
Conclusions:
- Guggulsterone (GS) demonstrates significant anticancer effects against human bladder cancer cells in vitro and in vivo.
- GS exhibits potential as a novel therapeutic agent for various grades of urothelial carcinoma.
