PUFAs enhance oxidative stress and apoptosis in tumour cells exposed to hypericin-mediated PDT.
Since many studies have suggested the impact of dietary polyunsaturated fatty acids on cancer progression and prognosis, there is an assumption of possible pre-sensitizing effects of their application in combined treatment. The present work evaluates modulation of photodynamic therapy (PDT) with hypericin by pre-treatment with n-3 and n-6 fatty acids in HT-29 and HeLa tumour cells. We observed stimulation of cytotoxic effects by docosahexaenoic acid (n-3) and arachidonic acid (n-6) in several stages of action in both cell lines. Treatment with either fatty acids or photodynamic therapy alone induced apoptosis in a dose- and time-dependent manner; however the effect was even more striking in mutual combination applied as pre-treatment with fatty acids prior to photodynamic therapy. Moreover, the combination also induced changes in membrane lipid composition leading to alteration in cell membrane fluidity. Increased toxicity of combined treatment was also confirmed by the presence of oxidative stress demonstrated by ROS production, RNS accumulation and increased presence of lipoperoxides. In conclusion, we suggest that pre-treatment with polyunsaturated fatty acids may contribute to cytotoxic effects induced by photodynamic therapy with hypericin.
Kello
Martin
M
Institute of Biology and Ecology, Faculty of Science, P. J. Safárik University in Kosice, Moyzesova 11, 040 01, Kosice, Slovakia.
Mikes
Jaromír
J
Jendzelovský
Rastislav
R
Koval
Ján
J
Fedorocko
Peter
P
D000873:Anthracenes; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D016718:Arachidonic Acid / Q000633:toxicity; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D004281:Docosahexaenoic Acids / Q000633:toxicity; D005231:Fatty Acids, Unsaturated / Q000633:toxicity*; D019073:HT29 Cells; D006801:Humans; D008560:Membrane Fluidity; D018384:Oxidative Stress; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010778:Photochemotherapy
D000873:Anthracenes; D000970:Antineoplastic Agents; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D010569:Perylene; C004965:hypericin