Influence of N atom number and form on the photodynamic activities of zinc phthalocyanines

2016 ◽  
Vol 20 (05) ◽  
pp. 602-614
Author(s):  
Wei W. Jin ◽  
Yue Wang ◽  
Ao Wang ◽  
Lin Zhou ◽  
Yun Lin ◽  
...  

Amino group modified phthalocyanines (Pcs) and their derivatives have attracted great attention in the field of photodynamic therapy (PDT) because of their satisfied anticancer activity. The existence of N atoms in these Pcs is very important because they not only provide water solubility of Pcs, but also greatly affect their PDT activity. To clear the influence of N atoms number on PDT activity of amino group modified Pcs and their derivatives, in this manuscript, two series of amine modified Pcs with different N atom number and their water soluble derivatives, hydrochloride and quaternizing derivatives were synthesized. Their photochemical and photobiology properties were studied and compared. The results indicated that with increasing the number on N atom, the reactive oxygen species (ROSs) generation ability, cancer cell uptaken ability and photoinduced anticancer activity were all increased in these ZnPcs.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Khatereh Khorsandi ◽  
Reza Hosseinzadeh ◽  
Elham Chamani

Abstract Background Melanoma as a type of skin cancer, is associated with a high mortality rate. Therefore, early diagnosis and efficient surgical treatment of this disease is very important. Photodynamic therapy (PDT) involves the activation of a photosensitizer by light at specific wavelength that interacts with oxygen and creates singlet oxygen molecules or reactive oxygen species (ROS), which can lead to tumor cell death. Furthermore, one of the main approches in the prevention and treatment of various cancers is plant compounds application. Phenolic compounds are essential class of natural antioxidants, which play crucial biological roles such as anticancer effects. It was previously suggested that flavonoid such as rutoside could acts as pro-oxidant or antioxidant. Hence, in this study, we aimed to investigate the effect of rutoside on the combination therapy with methylene blue (MB) assisted by photodynamic treatment (PDT) using red light source (660 nm; power density: 30 mW/cm2) on A375 human melanoma cancer cells. Methods For this purpose, the A375 human melanoma cancer cell lines were treated by MB-PDT and rutoside. Clonogenic cell survival, MTT assay, and cell death mechanisms were also determined after performing the treatment. Subsequently, after the rutoside treatment and photodynamic therapy (PDT), cell cycle and intracellular reactive oxygen species (ROS) generation were measured. Results The obtained results showed that, MB-PDT and rutoside had better cytotoxic and antiprolifrative effects on A375 melanoma cancer cells compared to each free drug, whereas the cytotoxic effect on HDF human dermal fibroblast cell was not significant. MB-PDT and rutoside combination induced apoptosis and cell cycle arrest in the human melanoma cancer cell line. Intracellular ROS increased in A375 cancer cell line after the treatment with MB-PDT and rutoside. Conclusion The results suggest that, MB-PDT and rutoside could be considered as novel approaches as the combination treatment of melanoma cancer.


2004 ◽  
Vol 279 (44) ◽  
pp. 45713-45720 ◽  
Author(s):  
Vicki Plaks ◽  
Yehudit Posen ◽  
Ohad Mazor ◽  
Alex Brandis ◽  
Avigdor Scherz ◽  
...  

Various forms of cellular stress induce adaptive responses through poorly understood mechanisms. In maintaining homeostasis, endothelial cells respond and adapt to changes in oxidative stress that prevail in the circulation. Endothelial cells are also the target of many oxidative stress-based vascular therapies. The objectives of this study were to determine whether endothelial cells adapt to oxidative stress induced upon the photosensitization of WST11 (a water-soluble Pd-bacteriochlorophyll derivative being developed as a photodynamic agent) and to study possible cellular mechanisms involved. The hallmark of WST11-based photodynamic therapy is thein situgeneration of cytotoxic reactive oxygen species causing vascular shutdown, hypoxia, and tumor eradication. Here we demonstrated that photodynamic therapy also induces adaptive responses and tolerance following a sublethal preconditioning of endothelial cells with the same (homologous) or different (heterologous) stressor. A link among p38 MAPK activity, expression of hsp70 and hsp27, and homologous adaptation to reactive oxygen species induced by photosensitized WST11 was established. In addition to characterization of some key proteins involved, our observations provide a beneficial new working tool for the studies of mechanisms involved in oxidative stress and adaptation using light-controlled photosensitization.


2021 ◽  
Author(s):  
Kaplan Kirakci ◽  
Tatyana Pozmogova ◽  
Andrey Y Protasevich ◽  
Georgy D Vavilov ◽  
Dmitri Stass ◽  
...  

X-ray-induced photodynamic therapy (X-PDT) has recently evolved into a suitable modality to fight cancer. This technique, which exploits radiosensitizers producing reactive oxygen species, allows for a reduction of the radiation...


Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 918 ◽  
Author(s):  
Hiromi Kurokawa ◽  
Hiromu Ito ◽  
Hirofumi Matsui

Photodynamic therapy (PDT) is a cancer treatment involving the generation of reactive oxygen species (ROS) by laser irradiation of porphyrins that accumulate in cancer tissues. 5-aminolevulinic acid (ALA), a porphyrin precursor, is often used as a photosensitizer. ALA is imported into cells via peptide transporter 1 (PEPT1), and porphyrin is exported via ATP-binding cassette member 2 of subfamily G (ABCG2). Thus, cancer cell-specific porphyrin accumulation involves regulation of both transporters to enhance the ALA-PDT effect. We reported previously that mitochondrial ROS (mitROS) upregulated PEPT1 expression and downregulated ABCG2 expression. Therefore, we propose that increasing mitROS production will enhance ALA-PDT cytotoxicity. Cisplatin is a chemotherapeutic drug that induces intracellular ROS generation. In this study, we investigated whether cisplatin-increased mitROS production in gastric cancer cell lines (RGK36 and RGK45) enhanced the cytotoxicity of ALA-PDT by regulation the expression of both PEPT1 and ABCG2. The results showed that cisplatin increased intracellular mitROS production in cancer but not normal cells (RGM1). PEPT1 was upregulated and ABCG2 downregulated in cancer cells treated with cisplatin. Moreover, intracellular porphyrin accumulation and ALA-PDT cytotoxicity increased. We conclude that cisplatin treatment increases the intracellular mitROS concentration and upregulates PEPT1 and downregulates ABCG2 expression.


2021 ◽  
Vol 22 (14) ◽  
pp. 7306
Author(s):  
Hiromi Kurokawa ◽  
Hiromu Ito ◽  
Hirofumi Matsui

In photodynamic therapy (PDT) for neoplasms, photosensitizers selectively accumulate in cancer tissue. Upon excitation with light of an optimal wavelength, the photosensitizer and surrounding molecules generate reactive oxygen species, resulting in cancer cell-specific cytotoxicity. Porphylipoprotein (PLP) has a porphyrin-based nanostructure. The porphyrin moiety of PLP is quenched because of its structure. When PLP is disrupted, the stacked porphyrins are separated into single molecules and act as photosensitizers. Unless PLP is disrupted, there is no photosensitive disorder in normal tissues. PLP can attenuate the photosensitive disorder compared with other photosensitizers and is ideal for use as a photosensitizer. However, the efficacy of PLP has not yet been evaluated. In this study, the mechanism of cancer cell-specific accumulation of PLP and its cytotoxic effect on cholangiocarcinoma cells were evaluated. The effects were investigated on normal and cancer-like mutant cells. The cytotoxicity effect of PLP PDT in cancer cells was significantly stronger than in normal cells. In addition, reactive oxygen species regulated intracellular PLP accumulation. The cytotoxic effects were also investigated using a cholangiocarcinoma cell line. The cytotoxicity of PLP PDT was significantly higher than that of laserphyrin-based PDT, a conventional type of PDT. PLP PDT could also inhibit tumor growth in vivo.


Author(s):  
Qian Wu ◽  
Youmei Li ◽  
Ying Li ◽  
Dong Wang ◽  
Ben Zhong Tang

Hydrogen peroxide (H2O2), as one kind of key reactive oxygen species (ROS), is mainly produced endogenously primarily in the mitochondria. The selective monitoring of H2O2 in living cells is of...


Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 93
Author(s):  
Bor-Chyuan Su ◽  
Giun-Yi Hung ◽  
Yun-Chieh Tu ◽  
Wei-Chen Yeh ◽  
Meng-Chieh Lin ◽  
...  

Synovial sarcoma is a rare but aggressive soft-tissue sarcoma associated with translocation t(X;18). Metastasis occurs in approximately 50% of all patients, and curative outcomes are difficult to achieve in this group. Since the efficacies of current therapeutic approaches for metastatic synovial sarcoma remain limited, new therapeutic agents are urgently needed. Tilapia piscidin 4 (TP4), a marine antimicrobial peptide, is known to exhibit multiple biological functions, including anti-bacterial, wound-healing, immunomodulatory, and anticancer activities. In the present study, we assessed the anticancer activity of TP4 in human synovial sarcoma cells and determined the underlying mechanisms. We first demonstrated that TP4 can induce necrotic cell death in human synovial sarcoma AsKa-SS and SW982 cells lines. In addition, we saw that TP4 initiates reactive oxygen species (ROS) production and downregulates antioxidant proteins, such as uncoupling protein-2, superoxide dismutase (SOD)-1, and SOD-2. Moreover, TP4-induced mitochondrial hyperpolarization is followed by elevation of mitochondrial ROS. Calcium overload is also triggered by TP4, and cell death can be attenuated by a necrosis inhibitor, ROS scavenger or calcium chelator. In our experiments, TP4 displayed strong anticancer activity in human synovial sarcoma cells by disrupting oxidative status, promoting mitochondrial hyperpolarization and causing calcium overload.


Drug Research ◽  
2019 ◽  
Vol 69 (10) ◽  
pp. 528-536
Author(s):  
Najat Bouchmaa ◽  
Reda Ben Mrid ◽  
Youness Boukharsa ◽  
Youssef Bouargalne ◽  
Mohamed Nhiri ◽  
...  

Abstract Background In cancer cells, the intracellular antioxidant capacity and the redox homeostasis are mainly maintained by the glutathione- and thioredoxin-dependent systems which are considered as promising targets for anticancer drugs. Pyridazinones constitute an interesting source of heterocyclic compounds for drug discovery. The present investigation focused on studying the in-vitro antitumor activity of newly synthesized Pyridazin-3(2h)-ones derivatives against P815 (Murin mastocytoma) cell line. Methods The in-vitro cytotoxic activities were investigated toward the P815 cell line using tetrazolium-based MTT assay. Lipid peroxidation and the specific activities of antioxidant enzymes were also determined. Results The newly compounds had a selective dose-dependent cytotoxic effect without affecting normal cells (PBMCs). Apoptosis was further confirmed through the characteristic apoptotic morphological changes and DNA fragmentation. Two compounds (6f and 7h) were highly cytotoxic and were submitted to extend biological testing to determine the likely mechanisms of their cytotoxicity. Results showed that these molecules may induce cytotoxicity via disturbing the redox homeostasis. Importantly, the anticancer activity of 6f and 7h could be due to the intracellular reactive oxygen species hypergeneration through significant loss of glutathione reductase and thioredoxin reductase activities. This eventually leads to oxidative stress-mediated P815 cell apoptosis. Furthermore, the co-administration of 6f or 7h with Methotrexate exhibited a synergistic cytotoxic effect. Conclusions considering their significant anticancer activity and chemosensitivity, 6f and 7h may improve the therapeutic efficacy of the current treatment for cancer.


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