Chlorophyll, chlorophyllin and related tetrapyrroles are significant inducers of mammalian phase 2 cytoprotective genes.
Plant chlorophylls and carotenoids are highly colored, conjugated polyenes that play central roles in photosynthesis. Other porphyrins (tetrapyrroles), such as cytochromes, which are structurally related to chlorophyll, participate in redox reactions in many living systems. An unexpected new property of tetrapyrroles, including tetramethyl coproporphyrin III, tetrabenzoporphine, copper chlorin e4 ethyl ester, and of carotenoids including zeaxanthin and alpha-cryptoxanthin is their ability to induce mammalian phase 2 proteins that protect cells against oxidants and electrophiles. The capacity of these compounds to induce the phase 2 response depends upon their ability or that of their metabolites to react with thiol groups, a property shared with all other classes of phase 2 inducers, which show few other structural similarities. Pseudo second-order rate constants of these inducers are correlated with their potency in inducing the phase 2 enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) in murine hepatoma cells. One of the most potent inducers was isolated from chlorophyllin, a semisynthetic water-soluble chlorophyll derivative. Although chlorophyll itself is low in inducer potency, it may nevertheless account for some of the disease-protective effects attributed to diets rich in green vegetables because it occurs in much higher concentrations in those plants than the widely studied 'phytochemicals'.
Fahey
Jed W
JW
Lewis B. and Dorothy Cullman Cancer Chemoprotection Center, Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21205-2185, USA. jfahey@jhmi.edu
Stephenson
Katherine K
KK
Dinkova-Kostova
Albena T
AT
Egner
Patricia A
PA
Kensler
Thomas W
TW
Talalay
Paul
P
D000818:Animals; D000975:Antioxidants / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002734:Chlorophyll / Q000494:pharmacology*; D002735:Chlorophyllides / Q000494:pharmacology*; D019610:Cytoprotection; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D008113:Liver Neoplasms / Q000473:pathology; D051379:Mice; D045725:Tetrapyrroles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D002735:Chlorophyllides; D045725:Tetrapyrroles; D002734:Chlorophyll; C007020:chlorophyllin