Inhibition of soybean lipoxygenase and mouse skin tumor promotion by onion and garlic components

Abstract

Onion and garlic essential oils were previously shown to inhibit mouse skin tumor promotion, as were the enzymes, lipoxygenase, and cyclooxygenase. In the present study, the inhibition of soybean lipoxygenase (EC 1.13.11.12) by onion and garlic components and related compounds was investigated. The IC50 values as well as the kinetic inhibition constants were determined for the most active compounds. Di-(1-propenyl) sulfide, an analog of the substrate moiety required for oxygenase action, was the only irreversible inhibitor observed with Ki = 59 microM and k3 = 0.53/min. Inhibition in the presence of substrate was uncompetitive at 88 and 132 microM linoleic acid with Ki = 129 microM. At 173 microM linoleic acid, however, inhibition was competitive with Ki = 66 microM. Dially trisulfide, allyl methyl trisulfide, and diallyl disulfide were competitive inhibitors, while 1-propenylpropyl sulfide and (E, Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide (ajoene) were mixed inhibitors. Nordihydroguaiaretic acid (NDGA), the most potent lipoxygenase inhibitor, was a competitive inhibitor with Ki = 0.29 microM. The results indicate a relative potency of inhibition for structural features in the following order: di(1-propenyl) sulfide greater than an alkenyl trisulfide greater than an alkenyl disulfide. Di(n-propyl) disulfide, a major onion oil component, inhibited neither lipoxygenase nor promotion. Di(1-propenyl) sulfide and ajoene inhibited both. This suggests that the inhibition of lipoxygenase may be involved in antipromotion.

Naturally occurring lignans efficiently induce apoptosis in colorectal tumor cells

“…Arachidonic acid metabolites like HETE have been identified as mediators of tumor growth and progression in various organs, such as skin or pancreas, and inhibitors of LOX prevent tumor development in these organs (Belman et al 1989;Ding et al 1999;Nakadate et al 1985). On the cellular level both down modulation of bcl 2 and activation of caspase 3 have been shown in vascular smooth muscle cells (Nishio and Watanabe 1997).…”

“…However, it was taken from the market because of possible toxic side effects (Gardner et al 1987). It is still widely used in experimental tumor models both as an inhibitor of LOX and as an inhibitor of tumor development in skin (Belman et al 1989;Wang et al 1991) and lung (Moody et al 1998).…”

“…In addition to its antioxidative effects, it inhibits lipoxygenase isoenzymes (LOX) (Ding et al 1999;Yamamoto et al 1987), transport channels (Wang et al 1993) and cellular respiration (Pavani et al 1994). Moreover, it was also shown to prevent both activation of carcinogens and tumor promotion in mouse skin (Belman et al 1989;Wang et al 1991) and in the bladder (Yu et al 1992). The latter effect was probably mediated by LOX inhibition.…”

Oxidative Stress and Antioxidant Herbs and Spices in Cancer Prevention

“…26 Onions and garlic are often used as food flavors and are used commonly in folk medicines in Asia and Africa. Belman et al 27 inhibitor; diallyl trisulfide, allyl methyl trisulfide, and diallyl disulfide were competitive inhibitors; and 1-propenylpropyl sulfide and (E, Z)-4,5,9 trithiadodeca-1,6,11-triene 9-oxide (ajoene) were mixed inhibitors. Sendl et al 28 also studied lipoxygenase inhibitory activity of garlic.…”

A Rethinking on the Benefits and Drawbacks of Common Antioxidants and a Proposal to Look for the Antioxidants in Allium Products as Ideal Agents: A Review

“…It is also known that diallyl disulfide inhibits in vivo activation of nitrosamines. Unsaturated polysulfides found in allium principles inhibit tumor promotion [78][79][80] perhaps by enhancing glutathionedependent detoxification enzymes. Injection of tumor cells treated with garlic extract, induced tumor immunity in mice.…”