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Published on: November 27, 2016
Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways
Shumin Mu1, Xingsong Tian, Yongwei Ruan
1Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Abstract:
Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.
Insights
Diosgenin induces apoptosis in human thyroid cells stimulated by insulin-like growth factor-1 (IGF-1). This natural compound activates caspase cascades via both Fas-related and mitochondrial pathways, offering potential therapeutic insights.
Area of Science:
- Endocrinology
- Molecular Biology
- Cell Biology
Background:
- Insulin-like growth factor-1 (IGF-1) promotes thyroid cell proliferation and survival.
- Diosgenin, a plant-derived steroid, typically induces apoptosis but spares thyroid cells.
- Previous studies showed IGF-1 upregulates cyclin D and FLIP, inhibiting apoptosis.
Purpose of the Study:
- To investigate the apoptotic effect of diosgenin on IGF-1-stimulated primary human thyrocytes.
- To elucidate the underlying molecular mechanisms of diosgenin-induced apoptosis in this context.
Main Methods:
- Primary human thyrocytes were pre-incubated with IGF-1.
- Cells were subsequently treated with varying concentrations of diosgenin for different durations.
- Apoptosis induction, caspase activation, FLIP levels, ROS production, and Bcl-2/Bax balance were assessed.
Main Results:
- Diosgenin induced apoptosis in IGF-1-stimulated human thyrocytes in a dose-dependent manner.
- Apoptosis was mediated by the activation of caspase cascades.
- Diosgenin inhibited FLIP, activated caspase-8 (Fas pathway), increased ROS, modulated Bax/Bcl-2, and cleaved caspase-9 (mitochondrial pathway).
Conclusions:
- Diosgenin triggers apoptosis in IGF-1-stimulated human thyrocytes via two distinct caspase-dependent pathways.
- The Fas-related and mitochondrial apoptotic pathways are both implicated.
- These findings highlight diosgenin's potential in thyroid cell apoptosis modulation.
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Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...

