Essential role of p53 in phenethyl isothiocyanate-induced apoptosis

Chuanshu Huang, Wei-Ya Ma, Jingxia Li, Stephen S Hecht, Zigang Dong

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Abstract

Phenethyl isothiocyanate (PEITC) is a natural product that is among the most effective cancer chemopreventive agents known. Mechanistic studies indicate that the chemopreventive activity of PEITC is associated with its favorable modification of carcinogen metabolism and its induction of apoptosis. Here, we found that PEITC blocks tumor promoter (12-O- tetradecanoylphorbol-13-acetate or epidermal growth factor)-induced cell transformation in mouse epidermal JB6 cells, and this inhibitory activity on cell transformation is correlated with induction of apoptosis. Most importantly, apoptosis induction by PEITC occurs through a p53-dependent pathway. This was demonstrated not only by results that PEITC induction of p53 protein expression and p53-dependent transactivation but also by PEITC- induced apoptosis in p53 +/+ cells but not in p53 -/cells. In contrast, PEITC induced apoptosis in cells with both normal or deficient sphingomyelinase activity. Our results demonstrate for the first time that p53 elevation is required for PEITC-induced apoptosis, which may be involved in its cancer chemopreventive activity.

Original languageEnglish (US)
Pages (from-to)4102-4106
Number of pages5
JournalCancer Research
Volume58
Issue number18
StatePublished - Sep 15 1998

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Apoptosis
Carcinogens
Sphingomyelin Phosphodiesterase
phenethyl isothiocyanate
Tetradecanoylphorbol Acetate
Biological Products
Epidermal Growth Factor
Transcriptional Activation
Neoplasms
Proteins

Cite this

Essential role of p53 in phenethyl isothiocyanate-induced apoptosis. / Huang, Chuanshu; Ma, Wei-Ya; Li, Jingxia; Hecht, Stephen S; Dong, Zigang.

In: Cancer Research, Vol. 58, No. 18, 15.09.1998, p. 4102-4106.

Research output: Contribution to journalArticle

Huang, C, Ma, W-Y, Li, J, Hecht, SS & Dong, Z 1998, 'Essential role of p53 in phenethyl isothiocyanate-induced apoptosis', Cancer Research, vol. 58, no. 18, pp. 4102-4106.
Huang, Chuanshu ; Ma, Wei-Ya ; Li, Jingxia ; Hecht, Stephen S ; Dong, Zigang. / Essential role of p53 in phenethyl isothiocyanate-induced apoptosis. In: Cancer Research. 1998 ; Vol. 58, No. 18. pp. 4102-4106.
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