Catalytic therapy of cancer with porphyrins and ascorbate.
Catalytic therapy (CT) is a cancer treatment modality based on the generation of reactive oxygen species (ROS) using a combination of substrate molecules and a catalyst. The most frequently used substrate and catalyst pair is ascorbate/Co phthalocyanine (PcCo). In the present study, porphyrins containing transition metal ions as catalysts in place of PcCo were studied. Porphyrins that are expected to be as efficient as phthalocyanines, but may have fewer side effects, were analyzed. ROS production through the combined use of ascorbate and porphyrins decreased the number of breast cancer tumor cells by 20-40% after a single in vitro treatment, as compared to control cells. Treatment with ascorbate in conjunction with porphyrins stimulated apoptosis and disrupted the cell cycle. These treatments enhanced apoptosis by 20-40% when compared to treatments with ascorbate and porphyrins. In addition, the number of cells accumulating in the sub G0/G1 stage of the cell cycle increased from 3- to 10-fold, potentially reflecting that the treatment was highly effective in inducing DNA damage in the tumor cells, suggesting that porphyrins may be beneficial as a CT catalyst in the treatment of cancer.
Rozanova Torshina
Nadejda
N
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA. rozanovan@hotmail.com
Zhang
Jin Z
JZ
Heck
Diane E
DE
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002384:Catalysis; D045744:Cell Line, Tumor; D006801:Humans; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D011166:Porphyrins / Q000494:pharmacology*; D017382:Reactive Oxygen Species
D011166:Porphyrins; D017382:Reactive Oxygen Species; D001205:Ascorbic Acid