@article {Harris:2007:0008-4212:1124,
title = "Plant phenolics regulate neoplastic cell growth and survival: a quantitative structureactivity and biochemical analysis",
journal = "Canadian Journal of Physiology and Pharmacology",
parent_itemid = "infobike://cndscipub/cjpp",
publishercode ="cndscipub",
year = "2007",
volume = "85",
number = "11",
publication date ="2007-11-01T00:00:00",
pages = "1124-1138",
itemtype = "ARTICLE",
issn = "0008-4212",
eissn = "1205-7541",
url = "https://www.ingentaconnect.com/content/cndscipub/cjpp/2007/00000085/00000011/art00011",
author = "Harris, Cory S. and Mo, Fan and Migahed, Lamiaa and Chepelev, Leonid and Haddad, Pierre S. and Wright, James S. and Willmore, William G. and Arnason, John T. and Bennett, Steffany A.L.",
abstract = "The anti-tumour activities of many plant phenolics at high concentrations (>100mol/L) suggest their potential use as dietary supplements in cancer chemoprevention and cancer chemotherapy. However, it is not clear what impact phenolic compounds have at the physiological concentrations
obtained through consumption of high phenolic diets on neoplastic cells. In the present study, 54 naturally occurring phenolics were evaluated at physiologically relevant concentrations for their capacity to alter PC12 cell viability in response to serum deprivation, the chemotherepeutic agent
etoposide, and the apoptogen C2-ceramide. Surprisingly, novel mitogenic, cytoprotective, and antiapoptotic activities were detected. Quantitative structureactivity relationship modelling indicated that many of these activities could be predicted by compound lipophilicity, steric bulk,
and (or) antioxidant capacity, with the exception of inhibition of ceramide-induced apoptosis. Where quantitative structureactivity relationship analysis was insufficient, biochemical assessment demonstrated that the benzoate orsellinic acid blocked downstream caspase-12 activation
following ceramide challenge. These findings demonstrate substantive mitogenic, cytoprotective, and antiapoptotic biological activities of plant phenolics on neoplastic cells at physiologically relevant dietary concentrations that should be considered in chemopreventive and chemotherapeutic
strategies.Les activit{\’e}s anti-tumorales de nombreux compos{\’e}s ph{\’e}noliques v{\’e}g{\’e}taux {\‘a} concentrations {\’e}lev{\’e}es (>100 M) laissent entrevoir une utilisation possible comme suppl{\’e}ments alimentaires dans la chimiopr{\’e}vention
et la chimioth{\’e}rapie des cancers. Toutefois, ne sait pas exactement quel impact les compos{\’e}s ph{\’e}noliques aux concentrations physiologiques obtenues par une alimentation riche en ph{\’e}nols ont sur les cellules n{\’e}oplasiques. Dans la pr{\’e}sente {\’e}tude,
on a {\’e}valu{\’e} 54 compos{\’e}s ph{\’e}noliques naturels {\‘a} des concentrations physiologiques capables de modifier la viabilit{\’e} des cellules PC12 en r{\’e}ponse {\‘a} la privation de s{\’e}rum, {\‘a} lagent chimioth{\’e}rapeutique {\’e}toposide
et {\‘a} lapoptog{\‘e}ne C2-c{\’e}ramide. Fait {\’e}tonnant, on a d{\’e}tect{\’e} de nouvelles activit{\’e}s mitog{\’e}niques, cytoprotectrices et antiapopotiques. La mod{\’e}lisation de la relation structureactivit{\’e} quantitative (RSAQ) a indiqu{\’e}
que beaucoup de ces activit{\’e}s pouvaient {\^e}tre pr{\’e}dites par la lipophilicit{\’e}, lencombrement st{\’e}rique et lactivit{\’e} antioxydante des compos{\’e}s, ou les trois, {\‘a} lexception de linhibition de lapoptose induite
par le c{\’e}ramide. En compl{\’e}ment {\‘a} lanalyse RSAQ, l{\’e}valuation biochimique a d{\’e}montr{\’e} que lacide orsellinique (benzoate) a bloqu{\’e} lactivation en aval de la caspase 12 apr{\‘e}s l{\’e}preuve avec c{\’e}ramide.
Ces r{\’e}sultats d{\’e}montrent que les compos{\’e}s ph{\’e}noliques v{\’e}g{\’e}taux ont des activit{\’e}s biologiques mitog{\’e}niques, cytoprotectrices et antiapoptotiques significatives sur les cellules n{\’e}oplasiques aux concentrations alimentaires physiologiquement
pertinentes, et quelles devraient {\^e}tre consid{\’e}r{\’e}es dans les strat{\’e}gies chimiopr{\’e}ventives et chimioth{\’e}rapeutiques.",
}