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PHOTODESTRUCTION OF TUMOR CELLS BY INDUCTION OF ENDOGENOUS ACCUMULATION OF PROTOPORPHYRIN IX: ENHANCEMENT BY 1, 10‐PHENANTHROLINE
Author(s) -
Rebeiz Natalie,
Rebeiz Carole C.,
Arkins Sean,
Kelley Keith W.,
Rebeiz Constantin A.
Publication year - 1992
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/j.1751-1097.1992.tb04258.x
Subject(s) - protoporphyrin ix , protoporphyrin , endogeny , concanavalin a , biochemistry , chemistry , biosynthesis , heme , in vitro , cell culture , incubation , microbiology and biotechnology , porphyrin , biology , enzyme , photodynamic therapy , organic chemistry , genetics
— Rapidly proliferating transformed mammalian cells can be photodesroyed in vitro upon inducing the accumulation of endogenous protoporphyrin IX (Proto). Proto biosynthesis and accumulation were triggered by manipulation of the porphyrin‐heme biosynthetic pathway. Proto accumulation in cultured cells was induced by treatment with 1.0 m M δ‐aminolevulinic acid (ALA), a naturally occurring 5‐carbon amino acid, for 3.5 h. In darkness, significant Proto accumulation became evident within 3.5 h of incubation. In the light, the accumulated tetrapyrroles triggered destruction of treated cells within the first 30 min of illumination, probably via the rapid oxidation of cellular constituents by singlet oxygen. Protoporphyrin IX accumulation and specific cell lysis increased significantly by inclusion of 0.75 m M 1,10‐phenanthroline (Oph), a tetrapyrrole biosynthesis modulator. Slower growing untransformed cells did not accumulate significant amounts of Proto following ALA and Oph treatment unless stimulated to proliferate with the mitogenic lectin Concanavalin A.