The dietary isothiocyanates and cancer chemopreventive agents phenethyl isothiocyanate and allyl isothiocyanate and their cysteine conjugates inhibited the growth and induced apoptosis of human leukaemia HL60 (p53-) and human myeloblastic leukaemia-1 cells (p53+) in vitro. The median growth inhibitory concentration (GC(50)) values were in the range 1.49-3.22 µM in cultures with 10% serum. Isothiocyanates and cysteine conjugates had increased potency against HL60 cells in serum-free medium, with GC(50) values of 0.8-0.9 µM. The potency of the compounds decreased with increased serum content of the medium, but that of the cysteine conjugates decreased more markedly. Growth inhibition and toxicity was characterised by either a rapid interaction of the isothiocyanate with the cells in the first hour of culture or exposure to isothiocyanate liberated from the cysteine conjugate in the initial 3 hr of culture, inhibition of macromolecule synthesis, and a commitment to apoptosis which developed in the initial 24 hr. Activities of caspase-3 and caspase-8 were increased during isothiocyanate-induced apoptosis, but caspase-1 activity was not. The general caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone and the specific caspase-8 inhibitor N-benzyloxycarbonyl-Ile-Glu(OMe)-Thr-Asp(OMe)-fluoromethylketone inhibited apoptosis, but specific caspase-1 and caspase-3 inhibitors did not. The antiproliferative activities were limited by hydrolysis of the isothiocyanate. This suggests that caspase-8 has a critical role, and caspase-3 a supporting role, in isothiocyanate induced apoptosis in which p53 is not an obligatory participant. Isothiocyanate-induced apoptosis may suppress the growth of preclinical rumours and contribute to the well-established decreased cancer incidence associated with a vegetable-rich diet.<\/p>\n","protected":false},"template":"","mots_cles":[],"class_list":["post-57489","resume","type-resume","status-publish","hentry"],"acf":{"adresse":"\"THORNALLEY PJ,UNIV ESSEX,DEPT BIOL SCI;CENT CAMPUS WIVENHOE PK;COLCHESTER CO4 3SQ,ESSEX ENGLAND.thorp@essex.ac.uk \"","annee":"2000","mois":"7","numero":"60:2","page":"221-231","auteurs":[{"ID":47995,"post_author":"0","post_date":"2018-12-04 04:25:38","post_date_gmt":"2018-12-04 03:25:38","post_content":"","post_title":"Thornalley","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"thornalley","to_ping":"","pinged":"","post_modified":"2018-12-04 04:25:38","post_modified_gmt":"2018-12-04 03:25:38","post_content_filtered":"","post_parent":0,"guid":"https:\/\/aprifel-pp.mentalworks.biz\/fr\/auteur\/thornalley\/","menu_order":0,"post_type":"auteur_resume","post_mime_type":"","comment_count":"0","filter":"raw"},{"ID":33563,"post_author":"0","post_date":"2018-12-04 00:14:43","post_date_gmt":"2018-12-03 23:14:43","post_content":"","post_title":"Kathleen Xu","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"kathleen-xu","to_ping":"","pinged":"","post_modified":"2018-12-04 00:14:43","post_modified_gmt":"2018-12-03 23:14:43","post_content_filtered":"","post_parent":0,"guid":"https:\/\/aprifel-pp.mentalworks.biz\/fr\/auteur\/kathleen-xu\/","menu_order":0,"post_type":"auteur_resume","post_mime_type":"","comment_count":"0","filter":"raw"}],"sources":[{"ID":46946,"post_author":"0","post_date":"2018-12-04 04:09:33","post_date_gmt":"2018-12-04 03:09:33","post_content":"","post_title":"BIOCHEMICAL PHARMACOLOGY","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"biochemical-pharmacology","to_ping":"","pinged":"","post_modified":"2018-12-04 04:09:33","post_modified_gmt":"2018-12-04 03:09:33","post_content_filtered":"","post_parent":0,"guid":"https:\/\/aprifel-pp.mentalworks.biz\/fr\/source\/biochemical-pharmacology\/","menu_order":0,"post_type":"source","post_mime_type":"","comment_count":"0","filter":"raw"}]},"yoast_head":"\n