Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line

Xiu-Ying Lin1, Chun-Di He, Ting Xiao

  • 1Department of Dermatology, No. 1 Hospital of China Medical University, Key Laboratory of Immunodermatology, Ministry of Health (China Medical University), Shenyang, China.

Insights

Acitretin effectively inhibits skin squamous cell carcinoma (SCC) growth by inducing apoptosis in cancer cells. This retinoid targets cancer cells via the CD95 apoptosis pathway, sparing normal skin cells.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Skin cancers represent the most frequent human malignancies.
  • Retinoids demonstrate potential in preventing and treating various human cancers.

Purpose of the Study:

  • To investigate the apoptosis-inducing effects of acitretin on human skin squamous cell carcinoma (SCC) SCL-1 cells.
  • To determine if acitretin affects non-malignant keratinocytes.

Main Methods:

  • Cell viability assays (enzyme-linked immunosorbent assay, AnnexinV/propidium iodide).
  • Morphological observation of apoptosis.
  • Western blotting for caspase activation (caspase-8, -9, -3, PARP).
  • Analysis of death receptor pathway components (CD95, CD95-ligand, FADD) and functional blocking with anti-Fas antibody.

Main Results:

  • Acitretin inhibited SCL-1 cell growth dose- and time-dependently, without affecting HaCaT keratinocytes.
  • Apoptosis induction was confirmed by multiple assays and involved caspase-8, -9, -3, and PARP activation.
  • Acitretin upregulated CD95, CD95-ligand, and FADD, and apoptosis was blocked by anti-Fas antibody, indicating involvement of the CD95 pathway.

Conclusions:

  • Acitretin induces apoptosis in human skin SCC cells.
  • The mechanism involves the CD95 death receptor pathway.
  • Acitretin exhibits selective toxicity towards skin cancer cells, sparing normal keratinocytes.

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