Ascorbic acid suppresses cell death in rat DS-sarcoma cancer cells induced by 5-aminolevulinic acid-based photodynamic therapy.
Especially in the public, vitamin C is considered supportive for the treatment of cancer and supplementation is common. However, the underlying mechanism that most chemotherapeutic agents, ionizing radiation, and photodynamic therapy exert on tumor cell kill is an increased production of reactive oxygen species (ROS) leading to irreversible tissue injury. Therefore, antioxidants like ascorbic acid (AA) may prevent cancer cells of cellular free radical damage and may therefore be contraindicated in patients undergoing tumor treatment. We report on the effects of AA on markers of oxidative stress and apoptosis in rat DS-sarcoma cells on 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). AA dose-dependently protected cancer cells against lipid and protein oxidation caused by ALA-PDT treatment. By real-time RT-PCR analysis an impressive increase of FasL (124-fold) and TNF-alpha (121-fold) mRNA was detected after PDT treatment. In addition, a decrease in mitochondrial transmembrane potential followed by the mitochondrial release of apoptosis-inducing factor (AIF) was observed. All these early signs of apoptosis were significantly reduced by AA, resulting in a 2.1-fold increased cell survival rate on ALA-PDT treatment. In conclusion, AA functions as a potent antioxidant, protecting mitochondria and other cell structures of oxidative cell injury induced by ALA-PDT and may therefore be contraindicated in patients undergoing tumor treatment.
Frank
Juergen
J
Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany. frank140@uni-hohenheim.de
Flaccus
Andrea
A
Schwarz
Christine
C
Lambert
Christine
C
Biesalski
Hans K
HK
D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D000075202:Contraindications; D015536:Down-Regulation; D053222:Fas Ligand Protein; D050356:Lipid Metabolism / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects; D010778:Photochemotherapy; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000235:genetics; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D051033:Apoptosis Inducing Factor; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D000622:Aminolevulinic Acid; D001205:Ascorbic Acid