PHOTODYNAMIC EFFECTS OF HEMATOPORPHYRIN DERIVATIVE ON THE UPTAKE OF RHODAMINE 123 BY MITOCHONDRIA OF INTACT MURINE L929 FIBROBLASTS AND CHINESE HAMSTER OVARY Kl CELLS

Abstract

Abstract— It was shown that the cationic fluorescence probe rhodamine 123 accumulates in mitochondria of murine L929 fibroblasts and Chinese hamster ovary Kl epithelial cells due to the driving force of both plasma membrane and mitochondrial membrane potentials. Photodynamic treatment of L929 cells with hematoporphyrin derivative resulted in an increased uptake of rhodamine 123 and a diminished uptake of 1,1,3,3,3′,3′‐hexamethylindocarbocyanine iodide. This indicates a considerably increased mitochondrial membrane potential, which most likely is the result of a direct or secondary inhibition of the ATP‐synthetase, and a decreased plasma membrane potential. The oxygen consumption rate and the ATP level decreased due to photodynamic treatment. Post‐incubation of L929 cells subsequent to photodynamic treatment revealed that the uptake of rhodamine 123. the ATP content and the oxygen consumption rate were restored. For all parameters similar results were obtained with CHO‐K1 cells, with the exception that during post‐incubation the intracellular ATP content remained at the level reached after illumination. These results indicate that photodynamically induced disturbance of mitochondrial functions and the ATP level are not crucial for the loss of clonogenicity of L929 cells. In CHO‐K1 cells however, the continuously lowered ATP level may have detrimental consequences for cell survival. The photodynamic stimulation of the rhodamine 123 uptake may be a rather general phenomenon. Because rhodamine 123 exhibits a much higher toxicity towards carcinoma cells than towards other cells, a synergistic interaction between this drug and photodynamic therapy (PDT) may be anticipated, if PDT also stimulates mitochondrial rhodamine 123 accumulation in carcinoma in vivo.

Delta-aminolevulinic acid-mediated photosensitization of prostate cell lines: Implication for photodynamic therapy of prostate cancer

“…Mitochondria occupy 15-50% of the total cytoplasmic volume of most animal cells, and participate in more metabolic functions than any other organelle, and their proper function is essential to maintain normal cellular metabolism [29]. Mitochondria have been implicated as an important target of porphyrin-mediated PDT [30][31][32]. Our study provides further support to this concept.…”

“…PPIX is synthesized from ALA in the heme-biosynthesis pathway within the mitochondria [33], and PPIX cannot be produced in cells devoid of mitochondria, i.e., erythrocytes [34]. In addition, some porphyrins are lipophilic compounds that may concentrate selectively in the mitochondria [30][31][32]35]. This selectivity appears also to be related to the fact that mitochondria have specific mitochondrialporphyrin-receptors [36].…”

Effects of the inhibitors of energy metabolism, lonidamine and levamisole, on 5-aminolevulinic-acid-induced photochemotherapy

“…6). In accordance with results from treatment with HpD and light (Boegheim et al, 1988) the level of ATP was decreased and that of ADP increased immediately and transiently after ALA-PCT (Fig. 7).…”

Effects of the inhibitors of energy metabolism, lonidamine and levamisole, on 5‐aminolevulinic‐acid‐induced photochemotherapy

“…11). The intracellular content of ATP was also found to revert to control values after PCT with HpD in L 929 cells (Boegheim et a/., 1988). Thus, despite the obvious signs of early injury to mitochondria, no persistent decrease in the ATP level was observed at doses sufficient to inhibit respiration.…”