Reactive oxygen species (ROS) from both endogenous and exogenous sources can cause oxidative DNA damage and dysregulated cell signaling, which are involved in the multistage process of
carcinogenesis such as
tumor initiation, promotion and progression. A number of structurally different
anticarcinogenic agents inhibit
inflammation and
tumor promotion as they reduce ROS production and oxidative DNA damage. Evidence suggests that
porphyrins can interfere with the actions of various
carcinogens and
mutagens by forming face-to-face complexes and their antimutagenic or antigenotoxic effects may also be attributed to their
antioxidant activities. However, little is known regarding the anti-
tumor promoting potential and mechanism of the
porphyrin compounds. Based on our previous results on the inhibitory effects of
chlorophyllin (CHL),
hemin and
tetrakis(4-benzoic acid)porphyrin (TBAP) against two-stage mouse skin
carcinogenesis, we have investigated their anti-
tumor promoting mechanisms. In the present work, CHL,
hemin and TBAP reduced
superoxide anion generation by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated HL-60 cells and the production of
hydroxyl radicals by Fenton reaction.
Porphyrins exert a dose-related inhibition of his(+) reversion in Salmonella typhimurium TA102 induced by
tert-butylhydroperoxide (t-BOOH).
DNA strand breaks by ROS derived from H(2)O(2)/Cu(II) and the formation of
8-hydroxydeoxyguanosine (8-OH-dG) in
calf thymus DNA treated with H(2)O(2)/UV also were inhibited markedly by
porphyrins in a concentration-dependent manner. Furthermore, CHL,
hemin and TBAP decreased
myeloperoxidase (MPO) activity and H(2)O(2) formation as well as epidermal
ornithine decarboxylase (ODC) activity in mouse skin treated with TPA. These results demonstrate that the antioxidative properties of
porphyrins are important for inhibiting TPA-induced
tumor promotion.