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Butein induces apoptosis in human uveal melanoma cells through mitochondrial apoptosis pathway

Zhihua Cui1, E Song, Dan-Ning Hu

  • 1Department of Ophthalmology, The First Hospital, Jilin University, Changchun, China.

Current Eye Research
|May 15, 2012
PubMed
Abstract

Insights

Butein selectively induces apoptosis in human uveal melanoma cells by activating the intrinsic mitochondrial pathway. This natural compound shows potent cytotoxic effects on cancer cells while sparing healthy ocular cells.

Area of Science:

  • Ophthalmology
  • Oncology
  • Pharmacology

Background:

  • Uveal melanoma is a rare but aggressive intraocular malignancy.
  • Targeted therapies are crucial for improving patient outcomes.
  • Understanding the molecular mechanisms of potential therapeutic agents is essential.

Purpose of the Study:

  • To investigate the cytotoxic effects of butein on human uveal melanoma cells.
  • To elucidate the signaling pathways involved in butein-induced cell death.
  • To assess the selectivity of butein towards uveal melanoma cells compared to normal ocular cells.

Main Methods:

  • Human uveal melanoma cell lines (M17, SP6.5, C918), retinal pigment epithelial (RPE) cells, and scleral fibroblasts were treated with butein.
  • Cell viability was assessed using MTT assays.
  • Apoptosis, mitochondrial transmembrane potential, cytosol cytochrome c levels, and caspase activities (caspase-3, -8, -9) were measured.

Main Results:

  • Butein demonstrated dose-dependent cytotoxicity against all tested uveal melanoma cell lines (IC50 values ranging from 13.3 to 16.7 μM).
  • Lower concentrations of butein (10-30 μM) selectively reduced uveal melanoma cell viability without affecting RPE cells or fibroblasts.
  • Butein induced apoptosis, increased mitochondrial permeability, and elevated cytosol cytochrome c and caspase-9/-3 activities.

Conclusions:

  • Butein exhibits selective and potent pro-apoptotic effects on human uveal melanoma cells.
  • The mechanism involves the activation of the intrinsic mitochondrial pathway.
  • Butein represents a potential therapeutic candidate for uveal melanoma.

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