Synergistic anticancer activity of 1,25-dihydroxyvitamin D3 and immune cytokines: the involvement of reactive oxygen species

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.

Download Full-text

Reactive Oxygen Species-Mediated Apoptosis and Cytotoxicity of Newly Synthesized Pyridazin-3-Ones In P815 (Murin Mastocytoma) Cell Line

Drug Research ◽

10.1055/a-0762-3775 ◽

2019 ◽

Vol 69 (10) ◽

pp. 528-536

Author(s):

Najat Bouchmaa ◽

Reda Ben Mrid ◽

Youness Boukharsa ◽

Youssef Bouargalne ◽

Mohamed Nhiri ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Anticancer Activity ◽

Cell Line ◽

Cytotoxic Effect ◽

Redox Homeostasis ◽

Reactive Oxygen ◽

Cytotoxic Activities ◽

Oxygen Species ◽

P815 Cell

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.

Download Full-text

Sono-synthesis approach improves anticancer activity of ZnO nanoparticles: reactive oxygen species depletion for killing human osteosarcoma cells

Nanomedicine ◽

10.2217/nnm-2020-0427 ◽

2021 ◽

Vol 16 (8) ◽

pp. 657-671

Author(s):

Mansoureh Parsa ◽

Mohammad H Entezari ◽

Azadeh Meshkini

Keyword(s):

Reactive Oxygen Species ◽

Anticancer Activity ◽

Zno Nanoparticles ◽

Reactive Oxygen ◽

Oxygen Species ◽

Zno Nps ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells ◽

Tumor Selectivity ◽

Biological Tests

Aim: To investigate the effect of ultrasound during the synthesis of ZnO nanoparticles (NPs) on their anticancer activity. Materials & methods: ZnO NPs were synthesized in the presence and absence of ultrasonic irradiation. Biological tests were performed on human osteosarcoma cancer cells (Saos-2). Results: The sono-synthesized sample indicated higher cytotoxicity than the conventional one. (IC50 = 16.48 ± 0.41 μg/ml for sonochemical ZnO; 26.96 ± 0.33 μg/ml for conventional ZnO). Both sonochemical and conventional samples acted like antioxidants and reduced intracellular reactive oxygen species level. This reduction was more significant in cells treated with the sono-synthesized sample. The sono-synthesized ZnO NPs showed more tumor selectivity than the conventional sample. Conclusion: Sono-synthesis of ZnO NPs by a bath sonicator could improve their anticancer activity.

Download Full-text