title: The principal urinary metabolite of allyl isothiocyanate, N-acetyl-S-(N-allylthiocarbamoyl)cysteine, inhibits the growth and muscle invasion of bladder cancer.
abstract: Naturally occurring allyl isothiocyanate (AITC) was recently shown to be selectively delivered to bladder cancer tissue via urinary excretion and to inhibit bladder cancer growth and muscle invasion in an animal model. AITC is excreted in urine mainly as N-acetyl-S-(N-allylthiocarbamoyl)cysteine, more commonly known as the N-acetylcysteine conjugate (NAC-AITC). We show here that treatment of human bladder cancer UM-UC-3 cells or rat bladder cancer AY-27 cells with NAC-AITC at 15 μM results in significant inhibition of cell growth and proliferation, together with cell cycle arrest and apoptosis. We also show that NAC-AITC administered orally at 10 μmol/kg body wt inhibits cancer growth by 40% and muscle invasion by 49% in an orthotopic rat bladder cancer model. Furthermore, the anticancer activity of NAC-AITC is associated with the modulation of several important molecular targets, including downregulation of both α-tubulin and β-tubulin, activation of caspase-3 and downregulation of vascular endothelial growth factor. These results are similar to those shown previously for AITC and are consistent with the understanding that NAC-AITC is a carrier of AITC. Furthermore, comparison of the pharmacokinetic and physical properties of NAC-AITC with those of AITC suggests that NAC-AITC is superior to AITC for potential use for prevention and therapy of bladder cancer.
authors: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors: Arup
authors: A
authors: Bhattacharya
authors: Yun
authors: Y
authors: Li
authors: Feng
authors: F
authors: Geng
authors: Rex
authors: R
authors: Munday
authors: Yuesheng
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000652:urine; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology* / Q000652:urine*; D009361:Neoplasm Invasiveness; D051381:Rats; D011916:Rats, Inbred F344; D013859:Thiocarbamates / Q000494:pharmacology* / Q000652:urine*; D014404:Tubulin / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017879:Isothiocyanates; D013859:Thiocarbamates; D014404:Tubulin; D042461:Vascular Endothelial Growth Factor A; C091178:N-acetyl-S-(N-allylthiocarbamoyl)cysteine; C004471:allyl isothiocyanate; D053148:Caspase 3; D003545:Cysteine