Chemopreventive isothiocyanates induce apoptosis and caspase-3-like protease activity

Isothiocyanates exert strong anticarcinogenic effects in a number of animal models of cancer, presumably by modulation of xenobiotic-metabolizing enzymes, such as by inhibition of cytochrome P-450 and/or by induction of phase II detoxifying enzymes. Here, we report that phenethyl isothiocyanate and...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1998-02, Vol.58 (3), p.402-408
Main Authors: YU, R, MANDLEKAR, S, HARVEY, K. J, UCKER, D. S, KONG, A.-N. T
Format: Article
Language:English
Subjects:
Anticarcinogenic Agents - pharmacology
Antineoplastic agents
Apoptosis - drug effects
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Caspase 3
Caspases
Chemical agents
Chemotherapy
Cysteine Endopeptidases - biosynthesis
Cysteine Endopeptidases - genetics
Cysteine Proteinase Inhibitors - pharmacology
Enzyme Induction - drug effects
HeLa Cells - drug effects
Humans
Isothiocyanates - pharmacology
Medical sciences
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
Oligopeptides - pharmacology
Pharmacology. Drug treatments
Poly(ADP-ribose) Polymerases - metabolism
Thiocyanates - pharmacology
Tumors
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Isothiocyanates exert strong anticarcinogenic effects in a number of animal models of cancer, presumably by modulation of xenobiotic-metabolizing enzymes, such as by inhibition of cytochrome P-450 and/or by induction of phase II detoxifying enzymes. Here, we report that phenethyl isothiocyanate and other structurally related isothiocyanates, phenylmethyl isothiocyanate, phenylbutyl isothiocyanate, and phenylhexyl isothiocyanate, but not phenyl isothiocyanate induced apoptosis in HeLa cells in a time- and dose-dependent manner. Treatment with apoptosis-inducing concentrations of isothiocyanates also caused rapid and transient induction of caspase-3/CPP32-like activity. Furthermore, these isothiocyanates, except phenyl isothiocyanate, stimulated proteolytic cleavage of poly(ADP-ribose) polymerase, which followed the appearance of caspase activity and preceded DNA fragmentation. Pretreatment with a potent caspase-3 inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde inhibited isothiocyanate-induced caspase-3-like activity and apoptosis. These results suggest that isothiocyanates may induce apoptosis through a caspase-3-dependent mechanism. The induction of apoptosis by isothiocyanates may provide a distinct mechanism for their chemopreventive functions.
ISSN:0008-5472
1538-7445