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Synthetic retinoid CD437 promotes rapid apoptosis in malignant human epidermal keratinocytes and G 1 arrest in their normal counterparts
Author(s) -
Hail Numsen,
Lotan Reuben
Publication year - 2001
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/1097-4652(200101)186:1<24::aid-jcp1006>3.0.co;2-s
Subject(s) - apoptosis , retinoid , retinoic acid , keratinocyte , cycloheximide , cancer research , cell culture , biology , hacat , cell , squamous carcinoma , microbiology and biotechnology , chemistry , carcinoma , biochemistry , genetics
Four human cutaneous squamous cell carcinoma (SCC) cell lines and normal human epidermal keratinocyte (NHEK) cells from two donors were examined for sensitivity to the synthetic retinoid 6‐[3‐(1‐adamantyl)‐4‐hydroxyphenyl]‐2‐naphthalene carboxylic acid (CD437) alone or in combination with other agents. CD437 promoted rapid (within 2 h) apoptosis in SCC cells and G 1 arrest in NHEK cells. G 1 arrest in NHEK cells was sustained for 48 h while apoptosis occurred in approximately 60% of SCC cell after 24 h. Apoptosis could not be inhibited by nuclear retinoic acid receptor antagonists or cycloheximide, indicating CD437 was functioning in a receptor‐independent manner. All‐ trans retinoic acid not only failed to induce apoptosis in SCC cells even at 20‐fold higher concentration relative to the effective concentration of CD437; it also decreased the efficacy of CD437. Because of its differential effects on normal versus malignant keratinocytes, CD437 may be useful for the prevention or treatment of cutaneous SCC. J. Cell. Physiol. 186:24–34, 2001. © 2001 Wiley‐Liss, Inc.