Effects of photodynamic therapy on the endocytic pathway

Kessel, David; Price, Michael R.; Caruso, Joseph A.; Reiners, John J.

doi:10.1039/c0pp00276c

Cited by 17 publications

(23 citation statements)

References 25 publications

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“…We have reported that photodamage directed against lysosomes > mitochondria >> the ER could inhibit endocytic processes that require PI‐3K activity in the 1c1c7 murine hepatoma 8, while mitochondrial photodamage was more effective at inhibiting endocytosis in a murine leukemia cell line 9. We have now extended the latter studies to include other PDT targets.…”

Section: Introductionmentioning

confidence: 81%

“…When PI‐3K is inhibited, a series of cytoplasmic vacuoles form, derived from endocytosed plasma membrane whose normal processing is thereby blocked 6, 7. The mechanism was proposed to involve continued endocytic plasma membrane influx into endosomes while membrane traffic between late endosomes and lysosomes is blocked 8. The vacuoles, therefore, represent swollen late endosomes reflecting an inhibition of membrane traffic from endosomes to lysosomes 6.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of endocytic processes by photodynamic therapy

Kessel

2011

Lasers Surg. Med.

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Background and Objective Recent studies have demonstrated an effect of photodamage on the endocytic pathway involved in recycling of membrane components. Using a series of agents with known sub-cellular targets, we explored the determinants of photodynamic inhibition of endocytic processes in three cell lines: a murine leukemia, a murine hepatoma and a non-malignant epithelial cell line of human origin. Study Design/Materials and Methods The PI-3 kinase antagonist wortmannin blocks endosomal processing pathway dependent on this enzyme, providing an indication of the ‘flux’ of endocytosis. Microscopic observations were used to assess the effect of photodamage on this pathway. Photosensitizing agents specific for mitochondrial, endoplasmic reticulum (ER), lysosomal and endosomal photodamage were employed. Conclusions Sub-lethal photodamage directed against endosomes or lysosomes interrupted early steps in this endocytic process in the hepatoma cell line. A mechanism for these effects is proposed. Mitochondrial photodamage could interrupt endocytosis, but at levels that also induced apoptosis. ER photodamage did not affect endocytosis even at lethal levels. Somewhat similar results were obtained with other cell lines, but there were sufficient differences to indicate that the cell phenotype is, in part, a determinant of the endocytic response to PDT. Further work will be needed to delineate the role of these endocytic effects in the array of responses to photodynamic therapy.

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Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Inhibition of endocytic processes by photodynamic therapy

Kessel

2011

Lasers Surg. Med.

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“…This indicates a fast redistribution of the berberine in favor of mitochondria due to its release from LDL or its escape from early endocytosis compartments, during the first 15 minutes. Such behavior, leading to a specific mitochondrial accumulation, is almost classical for hydrophobic compound bearing cationic charges (Kessel et al, 2011(Kessel et al, , 2003Ma et al, 2013;Rodriguez et al, 2009). …”

Section: 4-subcellular Localization Of Berberine Within U87-mg Cellsmentioning

confidence: 98%

“…This point has to be taken into consideration with regards to the possible degradation of certain photosensitizers in lysosomes after endocytosis and their subsequent lack of activity. Moreover, the mitochondria are important targets in photodynamic therapy and many other hydrophobic cationic compounds have been designed to present such a behavior leading to this subcellular localization (Kessel et al, 2011(Kessel et al, , 2003Rodriguez et al, 2009). This point is well correlated with our results showing an increased photo-oxidation and a photo-induced decreased of glioma cell viability mediated by the LDL-preloaded berberine when targeted cells over-express receptor B/E.…”

Section: -Conclusionmentioning

confidence: 98%

Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins

Andreazza

Vevert-Bizet

Bourg-Heckly

et al. 2016

International Journal of Pharmaceutics

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Recent years have seen a growing interest in Berberine, a phytochemical with multispectrum therapeutic activities, as anti-tumoral agent for photodynamic therapy (PDT). In this context, low density lipoproteins (LDL) play a key role in the delivery of the photosensitizer in tumor cells. We correlate the physicochemical parameters of the berberine association to LDL with the influence of LDL-delivery on its accumulation in a glioma cell line and on its photo-induced activity in view of antitumor PDT. Our results evidence an important binding of 400 berberine molecules per LDL. Changes in berberine and apoprotein fluorescence suggest different fixation types, involving various LDL compartments including the vicinity of the apoprotein. The berberine association to LDL does not affect their recognition by the specific B/E receptors, of which over-expression increases the cellular uptake of LDL-preloaded berberine. Fluorescence microscopy evidences the mitochondrial labeling of the glioma model cells, with no significant modification upon LDL-delivery. Moreover, the cellular delivery of berberine by LDL increases its photocytotoxic effects on such cells. So, this research illustrates the potential of berberine as a photosensitizing agent for PDT, in particular due to their behavior towards LDL as plasma vehicles, and gives insights into its mechanisms of cell uptake.

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“…We have previously reported on the ability of PDT to interfere with membrane recycling [8]. This represents a new modality whereby photodamage can interfere with cellular functions.…”

Section: Introductionmentioning

confidence: 98%

Biological consequences of PDT: tying up the loose ends

2011

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While many of the determinants of photodynamic tumor eradication have been identified, the story is not yet complete. Fluorescent probes for reactive oxygen species (ROS) are seldom specific, and the role of different ROS in apoptosis vs. autophagy are not fully delineated. Moreover, the conflicting roles of autophagy as both a death and a survival pathway remain to be explained. Most tissue-culture studies are carried out in 20% oxygen although this is far in excess of the environment of malignant cells in vivo. And while apoptotic and/or autophagic death appears to account for the lethal effects of PDT, an effect on membrane recycling has now been identified. In this report, we summarize some recent experiments designed to examine the specificity of fluorescent ROS probes. We also demonstrate the ability of hydrogen peroxide to accelerate the autophagic response to PDT in an adhering cell line, the 1c1c7 murine hepatoma. In this cell line, autophagy appears to be a pro-survival mechanism since a sub-line (KD) depleted in a critical autophagy protein (atg7) was more responsive to PDT than wild-type (WT) cells. There are clearly multiple determinants of direct tumor cell kill by PDT that depend on the PDT target, the ROS produced and phenotypic variations.

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Effects of photodynamic therapy on the endocytic pathway

Cited by 17 publications

References 25 publications

Inhibition of endocytic processes by photodynamic therapy

Inhibition of endocytic processes by photodynamic therapy

Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins

Biological consequences of PDT: tying up the loose ends

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