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Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1.

Lin XY, He CD, Xiao T, Jin X, Chen J, Wang YK, Liu M, Wang KB, Jiang Y, Wei HC, Chen HD - J. Cell. Mol. Med. (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

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Effects of acitretin on cell growth of SCL-1 cells. (A) SCL-1 cells and HaCaT cells were treated with acitretin at five different concentrations for 3 days. (B) SCL-1 cells and HaCaT cells were treated with 10−5 M of acitretin for various times. Cell proliferation was assessed by MTT assay. Cell viability was estimated from the equation: % of cell viability = 100 × At/Ac, where At and Ac are the absorbencies in treated and control cultures, respectively. Data are shown as median of three different independent experiments (each with three cultures).
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fig01: Effects of acitretin on cell growth of SCL-1 cells. (A) SCL-1 cells and HaCaT cells were treated with acitretin at five different concentrations for 3 days. (B) SCL-1 cells and HaCaT cells were treated with 10−5 M of acitretin for various times. Cell proliferation was assessed by MTT assay. Cell viability was estimated from the equation: % of cell viability = 100 × At/Ac, where At and Ac are the absorbencies in treated and control cultures, respectively. Data are shown as median of three different independent experiments (each with three cultures).

Mentions: We investigated the effects of acitretin on cell proliferation in SCL-1 and HaCaT at five different concentrations of acitretin for 3 days and 10−5 M of acitretin for 1, 3, 5 days using a MTT assay (Fig. 1A and B). The results showed that acitretin inhibited cell growth of SCL-1 in a dose- and time-dependent manner. In contrast, acitretin exhibited a few inhibitory effects on the proliferation of HaCaT cells, indicating that acitretin showed less toxicity to non-malignant keratinocytes.


Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1.

Lin XY, He CD, Xiao T, Jin X, Chen J, Wang YK, Liu M, Wang KB, Jiang Y, Wei HC, Chen HD - J. Cell. Mol. Med. (2009)

Effects of acitretin on cell growth of SCL-1 cells. (A) SCL-1 cells and HaCaT cells were treated with acitretin at five different concentrations for 3 days. (B) SCL-1 cells and HaCaT cells were treated with 10−5 M of acitretin for various times. Cell proliferation was assessed by MTT assay. Cell viability was estimated from the equation: % of cell viability = 100 × At/Ac, where At and Ac are the absorbencies in treated and control cultures, respectively. Data are shown as median of three different independent experiments (each with three cultures).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4498944&req=5

fig01: Effects of acitretin on cell growth of SCL-1 cells. (A) SCL-1 cells and HaCaT cells were treated with acitretin at five different concentrations for 3 days. (B) SCL-1 cells and HaCaT cells were treated with 10−5 M of acitretin for various times. Cell proliferation was assessed by MTT assay. Cell viability was estimated from the equation: % of cell viability = 100 × At/Ac, where At and Ac are the absorbencies in treated and control cultures, respectively. Data are shown as median of three different independent experiments (each with three cultures).
Mentions: We investigated the effects of acitretin on cell proliferation in SCL-1 and HaCaT at five different concentrations of acitretin for 3 days and 10−5 M of acitretin for 1, 3, 5 days using a MTT assay (Fig. 1A and B). The results showed that acitretin inhibited cell growth of SCL-1 in a dose- and time-dependent manner. In contrast, acitretin exhibited a few inhibitory effects on the proliferation of HaCaT cells, indicating that acitretin showed less toxicity to non-malignant keratinocytes.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department 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.

Show MeSH
Related in: MedlinePlus