Isothiocyanates as novel cytotoxic and cytostatic agents: molecular pathway on human transformed and non-transformed cells.
Cancer chemoprevention is a new approach in the management of cancer. Traditional cytotoxic chemotherapeutic approaches cannot cure most advanced solid malignancies. Chemoprevention can be defined as the use of non-cytotoxic drugs and natural agents to block the progression to invasive cancer. Recently, isothiocyanates, natural products found in the diet of humans, has been shown to function as cancer chemopreventive agents. They are strong inhibitors of phase I enzymes and inducers of phase II enzymes. They can also induce apoptosis and modulate cell-cycle progression of highly proliferating cancer cells. This commentary will review the mechanism of apoptosis and growth inhibition mediated by different isothiocyanates. Particular attention will be given to the effects of the new isothiocyanate 4-(methylthio)butylisothiocyanate (MTBITC). Since selective targeting and low toxicity for normal host tissues are fundamental requisites for proposed chemopreventive agents, we will also review the effects of different isothiocyanates on non-transformed human cells.
Fimognari
Carmela
C
Department of Pharmacology, University of Bologna, I-40126, Italy. carmela.fimognari@unibo.it
Nüsse
Michael
M
Berti
Fausto
F
Iori
Renato
R
Cantelli-Forti
Giorgio
G
Hrelia
Patrizia
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology
C447639:4-(methylthio)-3-butenyl isothiocyanate; D000970:Antineoplastic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; C037152:isothiocyanic acid; C016766:sulforaphane