المؤلفون: Carsten Lange, Patrick J. Bednarski

المصدر: Photodiagnosis and Photodynamic Therapy. 36:102478

مصطلحات موضوعية: GPX1, medicine.medical_treatment, Biophysics, Apoptosis, Photodynamic therapy, Dermatology, medicine.disease_cause, Temoporfin, chemistry.chemical_compound, Glutathione Peroxidase GPX1, Cell Line, Tumor, medicine, Humans, Pharmacology (medical), chemistry.chemical_classification, Glutathione Peroxidase, Reactive oxygen species, Photosensitizing Agents, Hydrogen Peroxide, Cell cycle, Mesoporphyrins, Photochemotherapy, Oncology, chemistry, Cancer cell, Cancer research, Reactive Oxygen Species, Oxidative stress

الوصف: Background Due to an increased elimination of reactive oxygen species (ROS), in particular hydrogen peroxide (H2O2), overexpression of glutathione peroxidase 1 (GPX1) can lead to an attenuation of apoptosis and development of resistance in cancer cells, thereby promoting tumor cell survival. Consequently, GPX1 inhibitors have the potential to be used in cancer therapy as they support oxidative stress in cancer cells. Similarly, photodynamic therapy (PDT) induces oxidative stress in cancer cells by the formation of ROS upon illumination. Thus, both methods of treatment might act in synergy when used in combination. Methods To investigate this hypothesis, combinations of the known GPX1 inhibitors 9-chloro-6-ethyl-6H-[1,2,3,4,5]pentathiepino[6,7-b]indole (CEPI) or mercaptosuccinic acid (MSA) with PDT induced by the photosensitizer (PS) temoporfin (5,10,15,20-tetra(m-hydroxyphenyl)chlorin, mTHPC) were studied in vitro. This new combinatory approach was intended to accumulate ROS formed during PDT via blockage of GPX1-catalyzed H2O2 degradation, and thus to enhance PDT-induced phototoxicity. Five human cancer cell lines from tumor origins treatable with PDT were utilized to investigate ROS generation, apoptosis induction, and cell cycle distribution. Results Synergy was identified with both GPX1 inhibitors, but not in all cell lines. ROS levels were increased after combined treatment with mTHPC and CEPI, but not MSA, in some cell lines, indicating that oxidative stress and ROS accumulation were enhanced by CEPI. Surprisingly, enhanced apoptosis induction was also observed with MSA afterwards, suggesting that other pathways contributed to the initiation of apoptosis. Cell cycle analysis confirmed apoptosis induction via the detection of DNA fragmentation. Conclusion A combination of GPX1 inhibitors with mTHPC-PDT has the potential to generate synergistic effects and to increase overall phototoxicity, but the success of this combination approach was dependent on cancer type, and even antagonistic effects can occur.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85705d57cba3271f9b2aa1fdd04088f8Test
https://doi.org/10.1016Test/j.pdpdt.2021.102478

المؤلفون: Siva Sankar Murthy Bandaru, Christopher Horst Lillig, Patrick J. Bednarski, Muhammad Zubair, Steven Behnisch‐Cornwell, Carola Schulzke, Claudia Urbainsky, Martin Napierkowski, Lisa Wolff

المصدر: ChemMedChem. 15:1497-1497

مصطلحات موضوعية: Pharmacology, chemistry.chemical_classification, Membrane potential, GPX1, Glutathione peroxidase, Organic Chemistry, medicine.disease_cause, Biochemistry, Cell biology, chemistry, Apoptosis, Drug Discovery, Cancer cell, medicine, Molecular Medicine, DNA fragmentation, General Pharmacology, Toxicology and Pharmaceutics, Cytotoxicity, Oxidative stress

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::25a192debb204c604460d447d10687d3Test
https://doi.org/10.1002/cmdc.202000577Test

المؤلفون: Renate Grünert, Steffi Perfahl, Katharina Korpis, Aron F. Westendorf, Patrick J. Bednarski

المصدر: Philosophical transactions. Series A, Mathematical, physical, and engineering sciences. 371(1995)

مصطلحات موضوعية: Programmed cell death, Azides, Light, Stereochemistry, General Mathematics, General Physics and Astronomy, Antineoplastic Agents, chemistry.chemical_compound, Neoplasms, medicine, Animals, Humans, Platinum, chemistry.chemical_classification, Cisplatin, Reactive oxygen species, Photosensitizing Agents, Cell growth, Chemistry, General Engineering, Glutathione, In vitro, Photochemotherapy, Apoptosis, Cancer cell, medicine.drug

الوصف: Various Pt IV diazides have been investigated over the years as light-activatable prodrugs that interfere with cell proliferation, accumulate in cancer cells and cause cell death. The potencies of the complexes vary depending on the substituted amines (pyridine=piperidine>ammine) as well as the coordination geometry ( trans diazide> cis ). Light-activated Pt IV diazides tend to be less specific than cisplatin at inhibiting cancer cell growth, but cells resistant to cisplatin show little cross-resistance to Pt IV diazides. Platinum is accumulated in the cancer cells to a similar level as cisplatin, but only when activated by light, indicating that reactive Pt species form photolytically. Studies show that Pt also becomes attached to cellular DNA upon the light activation of various Pt IV diazides. Structures of some of the photolysis products were elucidated by LC–MS/MS; monoaqua- and diaqua-Pt II complexes form that are reactive towards biomolecules such as calf thymus DNA. Platination of calf thymus DNA can be blocked by the addition of nucleophiles such as glutathione and chloride, further evidence that aqua-Pt II species form upon irradiation. Evidence is presented that reactive oxygen species may be generated in the first hours following photoactivation. Cell death does not take the usual apoptotic pathways seen with cisplatin, but appears to involve autophagy. Thus, photoactivated diazido-Pt IV complexes represent an interesting class of potential anti-cancer agents that can be selectively activated by light and kill cells by a mechanism different to the anti-cancer drug cisplatin.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c9a071845d0ff4f69db6a5bf30df3493Test
https://pubmed.ncbi.nlm.nih.gov/23776289Test