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Ferrochelatase Deficiency Abrogated the Enhancement of Aminolevulinic Acid‐mediated Protoporphyrin IX by Iron Chelator Deferoxamine
Author(s) -
Palasuberniam Pratheeba,
Kraus Daniel,
Mansi Matthew,
Braun Alexander,
Howley Richard,
Myers Kenneth A.,
Chen Bin
Publication year - 2019
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13091
Subject(s) - protoporphyrin ix , deferoxamine , ferrochelatase , skbr3 , chemistry , cancer research , zinc protoporphyrin , heme , biochemistry , gene silencing , cancer cell , microbiology and biotechnology , cancer , enzyme , biology , photodynamic therapy , gene , human breast , organic chemistry , genetics
Aminolevulinic acid ( ALA ) is a prodrug that is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (Pp IX ) for tumor fluorescence detection and photodynamic therapy ( PDT ). The iron chelator deferoxamine ( DFO ) has been widely used to enhance Pp IX accumulation by inhibiting the iron‐dependent bioconversion of Pp IX to heme, a reaction catalyzed by ferrochelatase ( FECH ). Tumor response to DFO treatment is known to be highly variable, and some tumors even show no response. Given the fact that tumors often exhibit reduced FECH expression/enzymatic activity, we examined how reducing FECH level affected the DFO enhancement effect. Our results showed that reducing FECH level by silencing FECH in SkBr3 breast cancer cells completely abrogated the enhancement effect of DFO . Although DFO enhanced ALA ‐Pp IX fluorescence and PDT response in SkBr3 vector control cells, it caused a similar increase in MCF 10A breast epithelial cells, resulting in no net gain in the selectivity toward tumor cells. We also found that DFO treatment induced less increase in ALA ‐Pp IX fluorescence in tumor cells with lower FECH activity ( MDA ‐ MB ‐231, Hs 578T) than in tumor cells with higher FECH activity ( MDA ‐ MB ‐453). Our study demonstrates that FECH activity is an important determinant of tumor response to DFO treatment.