Imiquimod activates p53-dependent apoptosis in a human basal cell carcinoma cell line

Journal of Dermatological Science
Shi-Wei HuangJeng-Jer Shieh

Abstract

The tumor suppressor p53 controls DNA repair, cell cycle, apoptosis, autophagy and numerous other cellular processes. Imiquimod (IMQ), a synthetic toll-like receptor (TLR) 7 ligand for the treatment of superficial basal cell carcinoma (BCC), eliminates cancer cells by activating cell-mediated immunity and directly inducing apoptosis and autophagy in cancer cells. To evaluate the role of p53 in IMQ-induced cell death in skin cancer cells. The expression, phosphorylation and subcellular localization of p53 were detected by real-time PCR, luciferase reporter assay, cycloheximide chase analysis, immunoblotting and immunocytochemistry. Using BCC/KMC1 cell line as a model, the upstream signaling of p53 activation was dissected by over-expression of TLR7/8, the addition of ROS scavenger, ATM/ATR inhibitors and pan-caspase inhibitor. The role of p53 in IMQ-induced apoptosis and autophagy was assessed by genetically silencing p53 and evaluated by a DNA content assay, immunoblotting, LC3 puncta detection and acridine orange staining. IMQ induced p53 mRNA expression and protein accumulation, increased Ser15 phosphorylation, promoted nuclear translocation and up-regulated its target genes in skin cancer cells in a TLR7/8-independent manner...Continue Reading

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Citations

Mar 6, 2018·Human Vaccines & Immunotherapeutics·Jianwei YuanXiaosong Liu
Nov 4, 2017·The Journal of Dermatological Treatment·Alvin Lim
Feb 10, 2018·Cancer Cell International·Eva VillamónM Luisa Gil
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Oct 13, 2018·Scientific Reports·Qinlian HouDeguan Li
Apr 27, 2018·International Journal of Molecular Sciences·Edilane Rodrigues Dantas de AraújoSilvana Maria Zucolotto
Jun 18, 2017·Frontiers in Pharmacology·Huju ChiOu Sha
Jan 8, 2020·AAPS PharmSciTech·Luiza Abrahão FrankSilvia S Guterres
May 10, 2020·BioMed Research International·Yong LiuQueqiao Bian
Aug 23, 2020·Biomedicines·Shoib Sarwar SiddiquiCijo George Vazhappilly
Sep 24, 2020·Journal of Clinical Medicine·Mircea TampaMonica Neagu
Mar 22, 2021·The Journal of Investigative Dermatology·Shu-Hao ChangJeng-Jer Shieh
Feb 15, 2018·Seminars in Cell & Developmental Biology·Solana AlculumbreVassili Soumelis
May 3, 2021·International Journal of Pediatric Otorhinolaryngology·Tankut UzunErdost Yıldız
Jul 29, 2021·Journal of Drug Targeting·Yingying LiGuangxi Zhai

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