Related Experiment Video
Updated: Jul 3, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
Published on: August 2, 2021
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.
Abstract:
Skin cancers are by far the most common human malignancies. Retinoids have shown promising preventive and therapeutic effects against a variety of human malignancies. The aim of this study was to investigate the apoptosis-inducing effect of acitretin on human skin squamous cell carcinoma (SCC) SCL-1 cells. We found that acitretin preferentially inhibited the growth of SCL-1 cells in a dose- and time-dependent manner, but not of non-malignant keratinocyte HaCaT cells. This inhibition appeared to be due to induction of apoptosis as revealed by enzyme-linked immunosorbent assay. AnnexinV/propidium iodide assay and morphological observation confirmed the pro-apoptotic effect of acitretin on SCL-1 cells. We further demonstrated that apoptosis was induced within 1-2 days and involved activation of caspases-8, -9, -3 and poly (ADP-ribose) polymerase (PARP). Caspase-8 inhibitor effectively suppressed acitretin-induced apoptosis whereas caspase-9 inhibitor did not. Acitretin increased the levels of CD95 (Fas), CD95-ligand and Fas-associated death domain. Neutralizing ZB4 anti-Fas antibody significantly inhibited the apoptosis in SCL-1 cells induced by acitretin. These results suggest that acitretin is able to induce apoptosis in skin cancer cells possibly via death receptor CD95 apoptosis pathway without affecting the viability of normal keratinocyte.
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.
Related Concept Videos
The Intrinsic Apoptotic Pathway
The Extrinsic Apoptotic Pathway
Acne Infection
Cellular Injury V: Apoptosis and Autophagy
Apoptosis
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
