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.

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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