Intramitochondrial dyes allow selective in vitro photolysis of carcinoma cells.

Abstract

Carcinoma cell mitochondria preferentially accumulate and retain certain cationic dyes to a much greater extent than most normal cells. Thus, they can potentially serve as targets for highly selective photochemotherapy. We evaluated 10 rhodamine and cyanine dyes as carcinoma-specific mitochondrial photosensitizers in vitro. The most effective,

Photosensitizing dyes for the selection of nontumorigenic revertants from human lung cancer cell lines

“…EDKC binding to plastic surfaces was studied using dishes containing medium (without cells) as a control. Nonspecific uptake not dependent on membrane potentials has previously been shown to account for 1% or less of the total dye uptake, as measured on cells killed by freeze-thawing (9).…”

“…An EDKC-and light-free clonogenic assay was done in triplicate to control for clonogenic inhibition by dye in the absence of light. Light alone has previously been shown to have negligible effects on the colony-forming efficiency of carcinoma and noncarcinoma cells (9). After irradiation, the cells were washed with DPBS and placed in complete medium.…”

“…This report describes the feasibility of achieving selective carcinoma cell photolysis for nontumorigenic revenant selec tion by applying the protocols for EDKC-mediated photolysis, as given by Oseroff et al (9), to a series of human bronchial epithelial and pleural mesothelial cancer cell lines.…”

“…In the carcinoma lines, 0.1^M EDKC, combined with red light, caused marked in vitro photolysis of human bladder, squamous, and colon carcinomas, but the same protocol had only a minimal effect on human keratinocytes and on CV-1 cells. The cell-killing effect was postulated to be due to toxic or reactive products, generated by the photodecomposition of EDKC, that have the electron transport chain of mitochondria as their primary target (9).…”

Cancer — the mitochondrial connection

“…Phosphonium cations were the first described mitochondriotrophic cationic amphiphiles (Green & Evan 2002). Other important and popular mitochondriotrophics are rhodamine 123 , cyanine dyes (Oseroff et al 1986), victoria blue (Morgan et al 1998) and dequalinium chloride (Weiss et al 1987) and their derivatives. Mitochondriotrophics are characterized by two characteristics; firstly they are amphiphilic, secondly the entire structure has their π electron charge density extended over at least three atoms or more, i.e., having a delocalized positive charge hence called "delocalized cations" (Weissig & Torchilin 2001).…”