Enhanced Antitumor Activity against Melanoma Cancer Cells by Nitric Oxide Release and Photosensitized Generation of Singlet Oxygen from Ruthenium Complexes

Ramos, Loyanne Carla Barbosa; Marchesi, Mario; Callejon, Daniel R.; Dias‐Baruffi, Marcelo; Lunardi, Claure N.; Slep, Leonardo D.; Bendhack, Lusiane Maria; Silva, Roberto Santana da

doi:10.1002/ejic.201600217

Cited by 30 publications

(8 citation statements)

References 45 publications

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“…These observations provided new insights into the molecular mechanisms involving the cytotoxicity of PS2 for B16F10 cells, for PS2 , besides the effect of singlet oxygen. A synergistic effect may be involved with the production of peroxynitrite (OONO – ), which has been detected in the mitochondrial respiration process involving several biochemical pathways including nitration of tyrosine, ,, being a useful indicator of oxidative damage. The increase in 3-nitrotyrosine has been used as a footprint of OONO – production and may serve to identify the possibility of PS2 generating that species in cell milieu.…”

Section: Resultsmentioning

confidence: 99%

Comparison of the Photodynamic Action of Porphyrin, Chlorin, and Isobacteriochlorin Derivatives toward a Melanotic Cell Line

Castro

Ramos

Mesquita

et al. 2021

ACS Appl. Bio Mater.

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Melanoma is the most dangerous form of skin cancer, with an abrupt growth of its incidence over the last years. It is extremely resistant to traditional treatments such as chemotherapy and radiotherapy, but therapies for this cancer are gaining attention. Photodynamic therapy (PDT) is considered an effective modality to treat several types of skin cancers and can offer the possibility to treat one of the most aggressive ones: melanoma. In this work, the effect of PDT on a melanotic cell line (B16F10 cells) was assessed by exposing cultured cells to 5,10,15-tris(pentafluorophenyl)-20-(4pyridyl)porphyrin (PS1) and to its chlorin (PS2) and isobacteriochlorin (PS3) corresponding derivatives and red LED light (λ = 660 ± 20 nm). The PDT effect in the cells' viability was measured using the MTT assay. The cell apoptosis was quantified by flow cytometry, and the subcellular localization of the photosensitizer was determined by fluorescence microscopy. In addition, the ability of PS2 to generate superoxide radicals was qualitatively assessed by tyrosine nitration. The results show that the efficiency of the PDT process is dependent on the structure of the PS and on their ability to produce singlet oxygen. Besides that, the photoactivation efficiency is highly dependent on the cellular sublocalization of the PS and on its cellular uptake and singlet oxygen production. We also found that the resistant cell line B16F10 has distinctive chlorin, isobacteriochlorin, or porphyrin-specific resistance profiles. Furthermore, it is shown that the highly fluorescent chlorin derivative PS2 can also be considered in imaging diagnostics.

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Section: Resultsmentioning

confidence: 99%

Comparison of the Photodynamic Action of Porphyrin, Chlorin, and Isobacteriochlorin Derivatives toward a Melanotic Cell Line

Castro

Ramos

Mesquita

et al. 2021

ACS Appl. Bio Mater.

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“…Singlet oxygen, O 2 ( 1 Δ g ) or commonly 1 O 2 , corresponds to the first excited state of molecular oxygen, − which is very reactive and capable of damaging organic material and biological targets such as DNA, RNA, and proteins. , The generation of this species enables many applications in biology and medicine such as the photochemical synthesis of natural products and drugs, photodegradation of pollutants, − photoinactivation of bacteria, − and the abatement of cancer cells. − The latter is known as photodynamic therapy (PDT), which is a minimally invasive procedure approved for the treatment of several types of cancer. ,− This therapy requires the use of a photosensitizer (PS), the presence of oxygen, and light of an appropriate wavelength to excite the PS. 1 O 2 is generated through an energy exchange mechanism between the triplet excited state of the PS and molecular oxygen.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular Reversible On–Off Switch for Singlet Oxygen Using Cucurbit[n]uril Inclusion Complexes

et al. 2017

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A novel strategy to control the generation of singlet oxygen by a photosensitizer using cucurbit[n]urils inclusion complexes is shown herein, and the strategy has great potential for therapeutic applications. We show the basic requirements of the photosensitizer complexes in order to develop an on−off switch for singlet oxygen that is reversible using competitive binding. The supramolecular strategy proposed in this paper avoids complex synthetic schemes in order to activate or deactivate the photosensitizer as previous work has shown and supports the use of biocompatible materials. Mechanistic insights into the control over the generation of singlet oxygen are provided, which strongly emphasize the key role of the cucurbit[n]uril macrocycles in the stabilization or deactivation of the triplet excited state.

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“…One approach to minimize the adverse effects of JAK inhibitors, as well as other pharmacological agents, is to release them with light using caged compounds, composed of an active molecule linked to a photoremovable protecting group that prevents the drug from acting onto the target tissue. Upon irradiation with light of the proper wavelength, the active drug is liberated, and it exerts the desired action. − This strategy allows pharmacological modulation with precise temporal and spatial resolution, minimizing adverse effects produced by bulk administration of the active drug.…”

Section: Introductionmentioning

confidence: 99%

RuBi-Ruxolitinib: A Photoreleasable Antitumor JAK Inhibitor

Rafic,

Ma,

Shih

et al. 2024

J. Am. Chem. Soc.

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We describe the synthesis and biological testing of ruthenium-bipyridine ruxolitinib (RuBiRuxo), a photoreleasable form of ruxolitinib, a JAK inhibitor used as an antitumoral agent in cutaneous T-cell lymphomas (CTCL). This novel caged compound is synthesized efficiently, is stable in aqueous solution at room temperature, and is photoreleased rapidly by visible light. Irradiation of RuBiRuxo reduces cell proliferation and induces apoptosis in a light-and time-dependent manner in a CTCL cell line. This effect is specific and is mediated by a decreased phosphorylation of STAT proteins. Our results demonstrate the potential of ruthenium-based photocompounds and light-based therapeutic approaches for the potential treatment of cutaneous lymphomas and other pathologies.

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Enhanced Antitumor Activity against Melanoma Cancer Cells by Nitric Oxide Release and Photosensitized Generation of Singlet Oxygen from Ruthenium Complexes

Cited by 30 publications

References 45 publications

Comparison of the Photodynamic Action of Porphyrin, Chlorin, and Isobacteriochlorin Derivatives toward a Melanotic Cell Line

Comparison of the Photodynamic Action of Porphyrin, Chlorin, and Isobacteriochlorin Derivatives toward a Melanotic Cell Line

Supramolecular Reversible On–Off Switch for Singlet Oxygen Using Cucurbit[n]uril Inclusion Complexes

RuBi-Ruxolitinib: A Photoreleasable Antitumor JAK Inhibitor

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