Polyunsaturated but not Conjugated Linoleic Acid Supplementation of Leukemic U937 Cells Can Act as an Amplification Factor for Photofrin‐mediated Photodynamic Therapy

Abstract

Polyunsaturated fatty acids located in leukemia cell membranes are excellent targets for peroxidation. They can significantly enhance the effectiveness of Photofrin-mediated photodynamic therapy (PDT)-induced cell killing. In this study, the peroxidizability of conjugated fatty acid isomers (9c,11t-linoleic acid and 9c,11c-linoleic acid) and polyunsaturated fatty acids (PUFAs; linoleic acid, gamma-linolenic acid and arachidonic acid) with 2,2'-azo-bis(2-amidinpropane)dihydrochloride, soybean lipoxygenase and photomediated peroxidation are compared with each other. Peroxidation was determined using different methods: by means of gas chromatography to estimate the fatty acid (FA) consumption, by photometry for the level of FA peroxides or phospholipid peroxides and by definition of the content of malondialdehyde for thiobarbituric acid reactive substances (TBARS). The results suggest that the generation of oxidation products from individual FAs indicate a different formation rate of oxidation products. Radical FA peroxides were produced most by polyunsaturated arachidonic acid, followed by linoleic acid and gamma-linolenic acid, whereas conjugated FA isomers did not generate peroxides. Accordingly, the levels of lipid peroxides and TBARS were substantially increased after incorporation and oxidation of polyunsaturated FAs into U937 cells and could significantly enhance the effectiveness of Photofrin-PDT-induced cytotoxicity. The results showed that PUFA, but not conjugated FA supplementation of U937 cells, can act as a PDT amplification factor.

In Vitro and In Vivo Studies of the Utility of Dimethyl and Diethyl Carbaporphyrin Ketals in Treatment of Cutaneous Leishmaniasis

“…This indicates a selectivity of the compounds for these cell types. Such selectivity on U937 cells may be associated with the presence of polyunsaturated fatty acids (PFA) that are localized in the membrane of these tumoral cells, which constitute excellent targets for lipid peroxidation via photodynamic mechanisms (49).…”

PUFAs enhance oxidative stress and apoptosis in tumour cells exposed to hypericin-mediated PDT

“…In general, n-3 PUFAs inhibit tumour induction and growth, whereas n-6 PUFAs favour them. Begin et al 32 were the first to show that AA, the n-6 PUFA, can exert antitumour activity in the form of decreased cell viability. The effects of individual PUFAs 7,11,12,33,34 or mixtures of Although enhancement of PDT action by PUFAs has already been demonstrated for 5-aminolevulinic acid 31 and photofrin, 32 the effect of pre-treatment with dietary fats prior to hypericinmediated PDT has not been studied so far.…”

“…Begin et al 32 were the first to show that AA, the n-6 PUFA, can exert antitumour activity in the form of decreased cell viability. The effects of individual PUFAs 7,11,12,33,34 or mixtures of Although enhancement of PDT action by PUFAs has already been demonstrated for 5-aminolevulinic acid 31 and photofrin, 32 the effect of pre-treatment with dietary fats prior to hypericinmediated PDT has not been studied so far. Previous studies were mostly devoted to various aspects of fatty acid peroxidation, including formation and toxicity of final lipoperoxidation products, and basic effects on cellular and metabolic levels.…”