Porphyrin Photosensitization of Multi‐drug Resistant Cell Types

Kessel, David; Erickson, Cathy

doi:10.1111/j.1751-1097.1992.tb04253.x

Cited by 50 publications

(31 citation statements)

References 9 publications

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“…We therefore suggest that the resistance of the MES-SA/Dx5 cells to PDT cannot be attributed to the overexpression of P-gp, which is in accordance with other studies showing that chlorins and porphyrin-based photosensitizers are not substrates for P-gp (Capella and Capella, 2003). Previously, it was shown that murine leukemia P388/ADR cells were not cross-resistant to mesoporphyrin-PDT (Kessel and Erickson, 1992). However, later it was demonstrated that MDR cells can be cross-resistant to PDT because of impaired cellular accumulation of photosensitizers due to P-gp efflux pump activity (Kessel et al, 1994).…”

Section: Discussionsupporting

confidence: 73%

Photochemical Internalization of Therapeutic Macromolecular Agents: A Novel Strategy to Kill Multidrug-Resistant Cancer Cells

Selbo¹,

Weyergang²,

Bonsted

et al. 2006

The Journal of Pharmacology and Experimental Therapeutics

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Drug resistance is a major problem for chemotherapy. Entrapment of anticancer drugs in endolysosomal compartments or active extrusions by plasma membrane proteins of the ATPbinding cassette (ABC) superfamily are important resistance mechanisms. This study evaluated photochemical internalization (PCI) of membrane-impermeable macromolecules that are not the target of ABC drug pumps for treating multidrug-resistant (MDR) cancer cells. We used the drug-sensitive uterine fibrosarcoma cell line MES-SA and its MDR, P-glycoprotein (P-gp)-overexpressing derivative MES-SA/Dx5 with the photosensitizer disulfonated meso-tetraphenylporphine (TPPS 2a ) and broad spectrum illumination. The PCI of doxorubicin, the ribosome-inactivating protein gelonin and adenoviral transduction were assessed in both cell lines, together with the uptake and excretion of TPPS 2a and of two fluid phase markers easily detectable by fluorescence [lucifer yellow (LY) and fluorescein isothiocyanate (FITC)-dextran], as a model of gelonin uptake. Both cell lines were resistant to PCI of doxorubicin, but equally sensitive to PCI of gelonin, even though the endocytosis rates of LY and FITC-dextran were significantly lower in the MDR cells. In control studies, MES-SA/Dx5 cells were more resistant to photodynamic therapy (TPPS 2a ϩ light only). This was not mediated by P-gp, as there were no differences in the uptake and efflux of TPPS 2a between the cell lines. After adenoviral infection, PCI enhanced gene delivery in both cell lines. In conclusion, PCI of macromolecular therapeutic agents that are not targets of P-gp is a novel therapeutic strategy to kill MDR cancer cells.

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Section: Discussionsupporting

confidence: 73%

Photochemical Internalization of Therapeutic Macromolecular Agents: A Novel Strategy to Kill Multidrug-Resistant Cancer Cells

Selbo¹,

Weyergang²,

Bonsted

et al. 2006

The Journal of Pharmacology and Experimental Therapeutics

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“…Several authors evaluated the phototoxicity of a number of dyes in MDR cells, with very good results. For example, it was shown that MDR murine leukemia cells are not cross-resistant to photosensitization by mesoporphyrin [18]. The photodynamic efficacy of a monocationic porphyrin which is not recognized by the multidrug transporter in murine leukemia cells in culture and in fibrosarcomas in vivo was also studied [21].…”

Section: Pdt Of Mdr Tumor Cellsmentioning

confidence: 99%

A Light in Multidrug Resistance: Photodynamic Treatment of Multidrug-Resistant Tumors

Capella

2003

J Biomed Sci

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The major drawback of cancer chemotherapy is the development of multidrug-resistant (MDR) tumor cells, which are cross-resistant to a broad range of structurally and functionally unrelated agents, making it difficult to treat these tumors. In the last decade, a number of authors have studied the effects of photodynamic therapy (PDT), a combination of visible light with photosensitizing agents, on MDR cells. The results, although still inconclusive, have raised the possibility of treating MDR tumors by PDT. This review examines the growing literature concerning the responses of MDR cells to PDT, while stressing the need for the development of new photosensitizers that possess the necessary characteristics for the photodynamic treatment of this class of tumor.

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“…Talaporfi n-mediated PDT may have effi cacy in treating hepatocellular carcinoma, whereas Foscan ® looked promising in the treatment of pancreatic cancer (Kessel and Erickson 1992 ). In the case of prostate cancer, Foscan ® , Tookad Tookad, and Lutex Tookad, looked minimally invasive alternatives to surgery or radiotherapy , reducing the risk of the post-surgical side effects of incontinence and impotence.…”

Section: Clinical Pdt For Cancermentioning

confidence: 98%

“…This should be of special importance in elderly or debilitated patients who poorly tolerate more intensive therapeutic regimens. Moreover, considering its unique singlet oxygen-dependent cytotoxic effects, PDT can be safely combined with other antitumor treatments without the risk of inducing cross-resistance (Kessel and Erickson 1992 ). However, there have been few studies on combinations of PDT with standard antitumor regimens published to date (Zuluaga and Lange 2008 ).…”

Section: Pdt Combined To Other Treatment Modalities In Cancermentioning

confidence: 99%

Photodynamic Therapy for Cancer: Principles, Clinical Applications, and Nanotechnological Approaches

et al. 2014

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Photodynamic therapy (PDT) is based on photochemical processes between light and an exogenous photosensitizer (PS) localized at disease level. These components, tolerated singly by the cells, generate cytotoxic oxygen-based molecular species in proper dosage and concentration. Mechanistically it consists in three phases: excitation of PS, generation of toxic oxygen species, and cell death ( Fig. 5.1 ). In the fi rst phase, light of an appropriate wavelength, usually visible (VIS) or near-infrared (NIR), excites the PS molecules from the ground state to the excited singlet state. The radiation wavelength is usually chosen to coincide with the maximum absorption wavelength of the drug molecule. In analogy with many other fl uorescent molecules, PS can, at this stage, decay to its ground state with concomitant emission of light in the form of fl uorescence. On the other hand, the excited singlet state PS may also undergo a process known as intersystem crossing whereby the spin of the excited electron inverts to form a relatively more stable and long-lived excited triplet-state that has electrons which spin in a parallel conformation in the two highest occupied molecular orbitals. High quantum effi ciency for this transition is a key characteristic of a good PS. The PS in triplet state can either decay to the ground state or transfer electron/energy to the surroundings through two types of reactions. A type 1 process

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Porphyrin Photosensitization of Multi‐drug Resistant Cell Types

Cited by 50 publications

References 9 publications

Photochemical Internalization of Therapeutic Macromolecular Agents: A Novel Strategy to Kill Multidrug-Resistant Cancer Cells

Photochemical Internalization of Therapeutic Macromolecular Agents: A Novel Strategy to Kill Multidrug-Resistant Cancer Cells

A Light in Multidrug Resistance: Photodynamic Treatment of Multidrug-Resistant Tumors

Photodynamic Therapy for Cancer: Principles, Clinical Applications, and Nanotechnological Approaches

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