TY - CHAP
T1 - Chemoprotection against cancer by isothiocyanates
T2 - A focus on the animal models and the protective mechanisms
AU - Dinkova-Kostova, Albena T.
PY - 2013
Y1 - 2013
N2 - The isothiocyanates are among the most extensively studied chemoprotective agents. They are derived from glucosinolate precursors by the action of β-thioglucosidase enzymes (myrosinases). The Cruciferae family represents a rich source of glucosinolates. Notably, nearly all of the biological activities of glucosinolates, in both plants and animals, are attributable to their cognate hydrolytic products, and the isothiocyanates are prominent examples. In contrast to their relatively inert glucosinolate precursors, the isothiocyanates are endowed with high chemical reactivity, especially with sulfur-centered nucleophiles, such as protein cysteine residues. There are numerous examples of the chemoprotective effects of isothiocyanates in a number of animal models of experimental carcinogenesis at various organ sites and against carcinogens of several different types. It is becoming increasingly clear that this efficient protection is due to multiple mechanisms, including induction of cytoprotective proteins through the Keap1/Nrf2/ARE pathway, inhibition of proinflammatory responses through the NFκB pathway, induction of cell cycle arrest and apoptosis, effects on heat shock proteins, and inhibition of angiogenesis and metastasis. Because the isothiocyanates affect the function of transcription factors and ultimately the expression of networks of genes, such protection is comprehensive and long-lasting.
AB - The isothiocyanates are among the most extensively studied chemoprotective agents. They are derived from glucosinolate precursors by the action of β-thioglucosidase enzymes (myrosinases). The Cruciferae family represents a rich source of glucosinolates. Notably, nearly all of the biological activities of glucosinolates, in both plants and animals, are attributable to their cognate hydrolytic products, and the isothiocyanates are prominent examples. In contrast to their relatively inert glucosinolate precursors, the isothiocyanates are endowed with high chemical reactivity, especially with sulfur-centered nucleophiles, such as protein cysteine residues. There are numerous examples of the chemoprotective effects of isothiocyanates in a number of animal models of experimental carcinogenesis at various organ sites and against carcinogens of several different types. It is becoming increasingly clear that this efficient protection is due to multiple mechanisms, including induction of cytoprotective proteins through the Keap1/Nrf2/ARE pathway, inhibition of proinflammatory responses through the NFκB pathway, induction of cell cycle arrest and apoptosis, effects on heat shock proteins, and inhibition of angiogenesis and metastasis. Because the isothiocyanates affect the function of transcription factors and ultimately the expression of networks of genes, such protection is comprehensive and long-lasting.
KW - Glucosinolate
KW - Keap1
KW - NFκB
KW - NQO1
KW - Nrf2
KW - Phenethyl isothiocyanate
KW - Sulforaphane
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UR - http://www.scopus.com/inward/citedby.url?scp=84874500431&partnerID=8YFLogxK
U2 - 10.1007/128-2012-337
DO - 10.1007/128-2012-337
M3 - Chapter
C2 - 22752581
AN - SCOPUS:84874500431
SN - 9783642345746
VL - 329
T3 - Topics in Current Chemistry
SP - 179
EP - 202
BT - Topics in Current Chemistry
ER -