Photodynamic Therapy: The Sensitization of Cancer Cells to Light

Miller, Jennifer B.

doi:10.1021/ed076p592

Cited by 34 publications

(26 citation statements)

References 4 publications

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“…Photodynamic therapy (PDT) is a rapidly expanding therapeutic modality for the treatment of a number of diseases including cancer [ 1 - 3 ]. PDT employs a photosensitizer which, upon irradiation, produces singlet oxygen ( 1 O 2 ) that damages cells [ 4 , 5 ]. One major objective of PDT is the search of new photosensitizers with high water solubility, low dark cytotoxycity, high capacity to penetrate the plasma membrane and generate 1 O 2 , and an ability to interact with specific cellular targets [ 6 - 8 ].…”

Section: Introductionmentioning

confidence: 99%

Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and mechanistic in vitro studies

et al. 2014

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BackgroundPorphyrin TMPyP4 (P4) and its C14H28-alkyl derivative (C14) are G-quadruplex binders and singlet oxygen (1O2) generators. In contrast, TMPyP2 (P2) produces 1O2 but it is not a G-quadruplex binder. As their photosensitizing activity is currently undefined, we report in this study their efficacy against a melanoma skin tumour and describe an in vitro mechanistic study which gives insights into their anticancer activity.MethodsUptake and antiproliferative activity of photoactivated P2, P4 and C14 have been investigated in murine melanoma B78-H1 cells by FACS, clonogenic and migration assays. Apoptosis was investigated by PARP-1 cleavage and annexin-propidium iodide assays. Biodistribution and in vivo anticancer activity were tested in melanoma tumour-bearing mice. Porphyrin binding and photocleavage of G-rich mRNA regions were investigated by electrophoresis and RT-PCR. Porphyrin effect on ERK pathway was explored by Western blots.ResultsThanks to its higher lipophylicity C14 was taken up by murine melanoma B78-H1 cells up to 30-fold more efficiently than P4. When photoactivated (7.2 J/cm2) in B78-H1 melanoma cells, P4 and C14, but not control P2, caused a strong inhibition of metabolic activity, clonogenic growth and cell migration. Biodistribution studies on melanoma tumour-bearing mice showed that P4 and C14 localize in the tumour. Upon irradiation (660 nm, 193 J/cm2), P4 and C14 retarded tumour growth and increased the median survival time of the treated mice by ~50% (P <0.01 by ANOVA), whereas porphyrin P2 did not. The light-dependent mechanism mediated by P4 and C14 is likely due to the binding to and photocleavage of G-rich quadruplex-forming sequences within the 5′-untranslated regions of the mitogenic ras genes. This causes a decrease of RAS protein and inhibition of downstream ERK pathway, which stimulates proliferation. Annexin V/propidium iodide and PARP-1 cleavage assays showed that the porphyrins arrested tumour growth by apoptosis and necrosis. C14 also showed an intrinsic light-independent anticancer activity, as recently reported for G4-RNA binders.ConclusionsPorphyrins P4 and C14 impair the clonogenic growth and migration of B78-H1 melanoma cells and inhibit melanoma tumour growth in vivo. Evidence is provided that C14 acts through light-dependent (mRNA photocleavage) and light-independent (translation inhibition) mechanisms.

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Section: Introductionmentioning

confidence: 99%

Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and mechanistic in vitro studies

et al. 2014

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“…To this end, it was needed to have a PS/quencher system that would uniquely produce SO by the Type II mechanism for PDT applications. 12 It has been shown that SO is the responsible species for the selective destruction of malignant tumor cells, and it has been recognized that the therapeutic efficiency of PDT may be completely reversed depending on whether Type I or Type II mechanisms are operating. 13 Thus, it is imperative to have a PS/quencher pair system in which its main photooxygenation pathway would be of the Type II mechanism, which is well known to produce SO only.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Singlet Oxygen Production by Photodynamic Therapy and a Novel Method for Its Intracellular Measurement

Luengas

Marín²,

Aviles

et al. 2014

Cancer Biotherapy and Radiopharmaceuticals

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The generation of singlet oxygen (SO) in the presence of specific photosensitizers (PSs) or semiconductor quantum dots (QDs) and its application in photodynamic therapy (PDT) is of great interest to develop cancer therapies with no need of surgery, chemotherapy, and/or radiotherapy. This work was focused on the identification of the main factors leading to the enhancement of SO production using Rose Bengal (RB), and Methylene Blue (MB) as PS species in organic and aqueous mediums. Subsequently, the capacity of zinc oxide (ZnO), zinc sulfide (ZnS), and ZnO/ZnS core-shell QDs as well as manganese (Mn(+2)) doped ZnO and ZnS nanoparticles (NPs) as potential PS was also investigated. Many variable parameters such as type of quencher, PSs, NPs, as well as its different concentrations, light source, excitation wavelength, reaction time, distance from light source, and nature of solvent were used. The degradation kinetics of the quenchers generated by SO species and the corresponding quantum yields were determined by monitoring the photo-oxidation of the chemical quencher and measuring its disappearance by fluorometry and spectrophotometry in the presence of NPs. Small intracellular changes of SO induced by these metal Zn (zinc) NPs and PDT could execute and accelerate deadly programs in these leukemic cells, providing in this way an innovative modality of treatment. In order to perform further more specific in vitro cytotoxic studies on B-chronic lymphocytic leukemia cells exposed to Zn NPs and PDT, we needed first to measure and ascertain those possible intracellular SO variations generated by this type of treatment; for this purpose, we have also developed and tested a novel method first described by us.

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“…[1][2][3] PDT involves the systemic or topic administration of a photosensitizer which, activated by light, produces singlet oxygen and other reactive oxygen species (ROS) that cause irreversible photodamage to cancer cells. 4,5 The basic objective in PDT research is the search for new and efficient photosensitizers with desired properties such as minimum dark cytotoxycity, high capacity to generate singlet oxygen and ROS, greater retention in diseased tissues over healthy tissues, chemical stability and good cellular uptake. [6][7][8] Though a number of new phosensitisers have been proposed, [9][10][11][12][13] the one most widely used in clinic is Photofrin.…”

Section: Introductionmentioning

confidence: 99%

Evidence that photoactivated pheophorbide a causes in human cancer cells a photodynamic effect involving lipid peroxidation

Rapozzi¹,

Miculan²,

Xodo³

2009

Cancer Biology & Therapy

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Photodynamic therapy (PDT) is a treatment modality that uses a combination of a photosensitizer and light to induce a photokilling process in the tumor tissue. Recently we re-considered pheophorbide a (Pba), a second-generation photosensitizer that has not yet been thoroughly investigated. Here, we report that Pba irradiated at 14 J/cm(2) induces a strong photodynamic effect in four tumor cell lines, with IC(50) values ranging between 70 and 250 nM. The mechanism of phototoxicity has been investigated in HeLa (IC(50) = 150 nM) and HepG2 (IC(50) = 95 nM) cells. In both cell lines Pba induces lipid peroxidation, as indicated by a marked increase of malonyldialdehyde and oxidized C11 BODIPY(581/591). At high doses (>IC(50)), Pba arrests cell growth completely by activating apoptosis and/or necrosis, while at low doses (

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Photodynamic Therapy: The Sensitization of Cancer Cells to Light

Abstract: Photodynamic therapy, a promising, new approach for destroying malignant cells, takes advantage of light, oxygen, and a drug (photosensitizer) that preferentially localizes in rapidly growing cells.

Cited by 34 publications

References 4 publications

Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and mechanistic in vitro studies

Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and mechanistic in vitro studies

Enhanced Singlet Oxygen Production by Photodynamic Therapy and a Novel Method for Its Intracellular Measurement

Evidence that photoactivated pheophorbide a causes in human cancer cells a photodynamic effect involving lipid peroxidation

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