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

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.

All-transretinoic acid induces cell-cycle arrest in human cutaneous squamous carcinoma cells by inhibiting the mitogen-activated protein kinase-activated protein 1 pathway

“…Retinoids are known to induce apoptosis in various cancer cells. In a previous study, acitretin induced apoptosis in SCL‐1 cells via the CD95/CD95L apoptotic signalling pathway . However, in our study, 10 and 30 μmol/L ATRA caused a low level of apoptosis (< 10%), which may be due to the low concentration of ATRA we used.…”

Effects of Wannachawee Recipe with Antipsoriatic Activity on Suppressing Inflammatory Cytokine Production in HaCaT Human Keratinocytes

“…The methotrexate toxicity, ranging from the unpleasant to the fatal, has severely limited its dose and duration of treatment [ 21 , 22 ]. Moreover, in accordance with Lin et al, acitretin did not affect the viability of normal keratinocytes, but it was able to induce apoptosis in skin squamous cell carcinoma (SCL-1) cells [ 23 ]. In contrast, Liwei et al revealed that retinoids altered cell cycle distribution of tongue squamous cell carcinoma (Tca8113) cells by increasing G0/G-phase population, decreasing in S-phase population, and inhibiting of G1/S switching [ 24 ].…”

Eruptive postoperative squamous cell carcinomas exhibiting a pathergy-like reaction around surgical wound sites

“…Oral retinoids, in particular isotretinoin and acitretin, have proven efficacious in decreasing the frequency of SCCs arising in patients at high risk and may be a consideration in patients similar to patient 5 who exhibit sustained pathergy-like reactions of SCCs arising in postoperative sites. [45][46][47] The oral retinoids, although potentially helpful in this setting, are not without side effects and tolerability of the drugs may be limiting factors. 46,47 Conclusion…”