Serine Conjugates of Chlorophyll and Bacteriochlorophyll: Photocytotoxicity <i>in vitro</i> and Tissue Distribution in Mice Bearing Melanoma Tumors

Rosenbach-Belkin, Varda; Chen, L.; Fiedor, Leszek; Tregub, I.; Pavlotsky, Felix; Brumfeld, Vlad; Salomon, Yoram; Scherz, Avigdor

doi:10.1111/j.1751-1097.1996.tb02439.x

Cited by 76 publications

(68 citation statements)

References 31 publications

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“…The anti-tumor effects of BchlSer using a protocol with no injection-illumination time interval were ascribed mainly to the anti-vascular action of this treatment modality. 20 When tested under the same conditions in the same cells, 16 the new derivative used here, Pd-Bacteriopheophorbide (Pd-Bpheid) (Fig. 1) shows about 1,000-fold higher phototoxicity than Photosan and greater anti-tumor efficiency than Bchl-Ser.…”

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confidence: 98%

“…This value is about 100 times lower than that of the hematoporphyrin derivative Photosan. 16,17 When tested on melanoma xenografts in mice 18 -20 and DS sarcoma in rats, 21 over 80% of the tumors were cured after a single PDT session. The anti-tumor effects of BchlSer using a protocol with no injection-illumination time interval were ascribed mainly to the anti-vascular action of this treatment modality.…”

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confidence: 99%

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Local photodynamic therapy (PDT) of rat C6 glioma xenografts with Pd‐bacteriopheophorbide leads to decreased metastases and increase of animal cure compared with surgery

Schreiber

Gross

Brandis

et al. 2002

Intl Journal of Cancer

106

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Photodynamic therapy (PDT), locally applied to solid C6 rat glioma tumors in the foot of CD1 nude mice, eradicated the primary tumor and also decreased the rate of groin and lung metastases. Pd-Bacteriopheophorbide (Pd-Bpheid), a novel photosensitizer synthesized in our laboratory, was used in our study. The primary lesion in the hind leg was treated by an i.v. injection of 5 mg/kg of Pd-Bpheid and immediate illumination (650 -800 nm, 360 J/cm 2 ). This protocol and the surgical amputation of the leg were compared for local and metastasis responses. Following PDT, hemorrhage, inflammation with tumor necrosis and flattening were observed and histologically verified in the photodynamically treated tumor. Whereas local tumor control rates were up to 64% following PDT, in surgically treated animals, local tumor control was absolute. The rates of metastases in the groin and the lungs were at least 12-fold lower in the photodynamically treated animals compared with untreated or surgerytreated groups. The overall cure rates after PDT or surgery were 36% and 6%, respectively, at 8 weeks. These findings suggest that local PDT with Pd-Bpheid, which acts primarily on the tumor vasculature, efficiently eradicates the solid C6 tumors. In addition, the local PDT of the primary lesion has beneficial therapeutic effects on remote C6 metastasis, which is not obtained with surgery. It is therefore suggested, that although surgery is highly efficient for the immediate removal of the primary tumor, it lacks such systemic, therapeutic effects on distant metastases. Pd-Bpheid-PDT may thus offer a potentially superior curative therapy for C6 glioma tumors in the limb by eradicating the target tumor and by reducing the rate of metastasis in the groin and lung, possibly due to innate immunity. © 2002 Wiley-Liss, Inc. Key words: photodynamic therapy; surgery; Pd-bacteriopheophorbide; C6 glioma tumor; metastasisPhotodynamic therapy (PDT) is based on the destruction of tumors by cytotoxic reactive oxygen species (ROS) produced upon local tumor illumination in patients administered with a photosensitizer. 1-3 Following health agency approval for photofrin-based PDT in many countries, this anti-cancer treatment modality entered clinical use for the local treatment of an increasing number of indications including skin, esophageal, lung, gastric, cervical and bladder cancers. 4 PDT is usually considered a local anti-tumor treatment modality. However, reports from several laboratories suggest that PDT also induces beneficial systemic effects. Following in vitro hematoporphyrin-based PDT, adhesiveness and metastatic potential decline in DHD-K12-cultured colon carcinoma cells. Moreover, intravenous or s.c. injection of these PDT-treated cells to rats resulted in a reduced number of lung metastases compared with untreated cell injection. 5,6 Although this observation may be due to local photodynamic damage, the potential beneficial effect may be viewed as systemic. Other in vivo studies showed that local PDT with various photosensitizers mediates ...

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confidence: 98%

mentioning

confidence: 99%

Local photodynamic therapy (PDT) of rat C6 glioma xenografts with Pd‐bacteriopheophorbide leads to decreased metastases and increase of animal cure compared with surgery

Schreiber

Gross

Brandis

et al. 2002

Intl Journal of Cancer

106

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“…Of these, bacteriochlorophyll-serine (Bchl-ser) -the photosensitizer used in the present study -shows a number of features that underline the potential of soluble bacteriochlorophyll derivatives in tumour photodynamic therapy. These features include phototoxicity, which under in vitro conditions is approximately 200 times greater than the haematoporphyrin derivatives, strong absorption at 760 -80 nm (allowing deeper light penetration into tissues), rapid tissue clearance and minimal extravasation from the circulation (Rosenbach-Belkin et al, 1996).…”

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Combined hyperthermia and chlorophyll-based photodynamic therapy: tumour growth and metabolic microenvironment

et al. 2003

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The effects of combined and simultaneously applied localised 431C hyperthermia (HT) and an antivascular bacteriochlorophyllserine-based photodynamic therapy (Bchl-ser-PDT) on tumour growth and several microenvironmental parameters were examined. Rats bearing DS-sarcomas were allocated to treatment groups:The light source used was an infrared-A irradiator, which, by use of appropriate filters, delivered the different ranges of wavelengths required. Following treatment, tumour volume was monitored. The greatest tumour growth inhibition was seen with Bchl-ser-PDT þ HT, and subsequent experiments identified the pathophysiological basis for this effect. Red blood cell flux in tumour microvessels declined rapidly upon Bchl-ser-PDT þ HT, reaching approximately 10% of initial values by the end of treatment. Similarly, tumour oxygenation worsened, reaching almost anoxic levels by the end of the treatment period. Assessment of metabolic parameters showed a pronounced increase in lactate levels and a decrease in ATP concentrations after combined treatment. The results presented suggest that vascular collapse and flow stasis resulting in a deterioration of tumour oxygenation and a switch from oxidative to glycolytic glucose turnover are key elements in the tumour eradication seen with this novel approach in which an antivascular PDT and HT are combined and simultaneously applied.

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“…[5][6][7] In recent years, deeper insight into the mechanisms of metal ion -Chl interactions has become important also for the development of procedures for modification and synthesis of new tetrapyrrolic complexes in terms of their potential biomedical applications. [8][9][10] Although the primary function of chlorophylls is related to electron transfer processes, their occurrence in biological systems is not due to pigment interactions with redox-active metal ions. Properties of natural photosystems, including the composition of endogenous ligands, prevent degradation of the pigment's macrocyclic structure in the presence of Cu 2+ and other potential metallic oxidants.…”

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confidence: 99%

Fine tuning of copper(ii)–chlorophyll interactions in organic media. Metalation versus oxidation of the macrocycle

et al. 2015

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The nature of chlorophyll interactions with copper(II) ions varies considerably in organic solvents, depending on the dominant coordinative form. Besides formation of the metallo tetrapyrrolic complex, Cu(II) ions can cause oxidation of the pigment, reversible or irreversible, which can lead to the destruction of the macrocyclic structure. All these reaction types can be distinguished within a quite narrow range of reaction conditions. The ability to form new metallo derivatives in either metalation or transmetalation reactions is obviously limited by the concentration of the potential oxidant, but can be secured below this level via suitable composition of the reaction system. The decisive factor in the selection of a specific reaction pathway is the presence of a potential ligand that can affect the reactivity of Cu(II) for example by shifting its redox potential. Spectroscopic and electrochemical studies were performed in order to determine the predominant species of Cu(II) in methanol, nitromethane and acetonitrile in the presence of chloride and acetate ions, as well as to assign their appropriate oxidizing ability. This allowed us to estimate the boundary conditions for the electron transfer processes in chlorophyll-Cu(II) systems. Chlorophyll and its free base can undergo both types of electron transfer processes, however, they reveal different susceptibilities that make this class of ligands quite versatile markers in tuning the reactivity of metal ions in solutions. IntroductionInteractions of chlorophylls (Chls; including chlorophyll a, Chla, its free base pheophytin a, Pheoa, and other derivatives) with metal ions, although not strictly related to their basic biological functions, are important for proper metabolism of the photosynthetic pigment. They are decisive not only in biosynthesis of Chla (Fig. 1) at the stage of enzyme-driven Mg 2+ incorporation into protoporphyrin IX (3,7,12,17-tetramethyl-8,13-divinyl-2,18-porphinedipropionic acid), [1][2][3][4] but also in the spontaneous substitution of metal ions occurring in plants growing on soils contaminated by heavy metals. 5 The latter effect, observed clearly for Cu 2+ , Zn 2+ , Cd 2+ and Hg 2+ , results in the irreversible loss of photosynthetic abilities. [5][6][7] In recent years, deeper insight into the mechanisms of metal ion -Chl interactions has become important also for the development of procedures for modification and synthesis of new tetrapyrrolic complexes in terms of their potential biomedical applications. [8][9][10] Although the primary function of chlorophylls is related to electron transfer processes, their occurrence in biological systems is not due to pigment interactions with redox-active metal ions. Properties of natural photosystems, View Article OnlineView Journal | View Issue including the composition of endogenous ligands, prevent degradation of the pigment's macrocyclic structure in the presence of Cu 2+ and other potential metallic oxidants.Displacement of the chlorophyllic central ion in vivo is limited to a few me...

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Serine Conjugates of Chlorophyll and Bacteriochlorophyll: Photocytotoxicity in vitro and Tissue Distribution in Mice Bearing Melanoma Tumors

Cited by 76 publications

References 31 publications

Local photodynamic therapy (PDT) of rat C6 glioma xenografts with Pd‐bacteriopheophorbide leads to decreased metastases and increase of animal cure compared with surgery

Local photodynamic therapy (PDT) of rat C6 glioma xenografts with Pd‐bacteriopheophorbide leads to decreased metastases and increase of animal cure compared with surgery

Combined hyperthermia and chlorophyll-based photodynamic therapy: tumour growth and metabolic microenvironment

Fine tuning of copper(ii)–chlorophyll interactions in organic media. Metalation versus oxidation of the macrocycle

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