Blockage of JNK pathway enhances arsenic trioxide-induced apoptosis in human keratinocytes

Journal Article · Thu Apr 15 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.12.037· OSTI ID:21344925

Liu, Z -M; Hong, D -Y ^[1]

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1. Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)

Arsenic is well known as a carcinogen predisposing humans to some severe diseases and also as an effective medicine for treating acute promyelocytic leukemia, syphilis, and psoriasis. Multiple active mechanisms, including cell cycle arrest and apoptosis, have been proposed in therapy; however, the opposing effects of arsenic remain controversial. Our previous study found that arsenic trioxide (ATO)-induced activation of p21{sup WAF1/CIP1} (p21) led to A431 cell death through the antagonistic effects of the signaling of ERK1/2 and JNK1. In the current study, the inhibitory effects of JNK1 on ATO-induced p21 expression were explored. Over-expression of JNK1 in A431 cells could inhibit p21 expression, which was associated with HDAC1 and TGIF. Using the GST pull-down assay and fluorescence resonance energy transfer analysis, N-terminal domain (amino acids 1-108) of TGIF, critical to its binding with c-Jun, was found. Using reporter assays, requirement of the C-terminal domain (amino acids 138-272) of TGIF to suppress ATO-induced p21 expression was observed. Thus, the domains of TGIF that carried out its inhibitory effects on p21 were identified. Finally, treatment with JNK inhibitor SP600125 could enhance ATO-induced apoptosis of HaCaT keratinocytes by using flow cytometry.

• OSTI ID: 21344925
• Journal Information: Toxicology and Applied Pharmacology, Vol. 244, Issue 2; Other Information: DOI: 10.1016/j.taap.2009.12.037; PII: S0041-008X(10)00002-5; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
APOPTOSIS
ARSENIC
CARCINOGENS
CELL CYCLE
FLUORESCENCE
LEUKEMIA
MEN
PSORIASIS
SYPHILIS
THERAPY
ANIMALS
BACTERIAL DISEASES
CARBOXYLIC ACIDS
DISEASES
ELEMENTS
EMISSION
IMMUNE SYSTEM DISEASES
INFECTIOUS DISEASES
LUMINESCENCE
MALES
MAMMALS
MAN
MEDICINE
NEOPLASMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHOTON EMISSION
PRIMATES
SEMIMETALS
SKIN DISEASES
VERTEBRATES