scholarly journals 6‐Shogaol induces apoptosis in acute lymphoblastic leukaemia cells by targeting p53 signalling pathway and generation of reactive oxygen species

2021 ◽  
Author(s):  
Somayeh Najafi Dorcheh ◽  
Soheila Rahgozar ◽  
Daryush Talei
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Reactive Oxygen ◽  
Signalling Pathway ◽  
Oxygen Species

scholarly journals Reactive Oxygen Species in Acute Lymphoblastic Leukaemia: Reducing Radicals to Refine Responses

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1616
Author(s):  
Abdul Mannan ◽  
Zacary P Germon ◽  
Janis Chamberlain ◽  
Jonathan R Sillar ◽  
Brett Nixon ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Molecular Mechanisms ◽  
Chemotherapy Resistance ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Therapeutic Approaches ◽  
T Lymphoblasts

Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children and adolescents. Approximately 70% of patients survive >5-years following diagnosis, however, for those that fail upfront therapies, survival is poor. Reactive oxygen species (ROS) are elevated in a range of cancers and are emerging as significant contributors to the leukaemogenesis of ALL. ROS modulate the function of signalling proteins through oxidation of cysteine residues, as well as promote genomic instability by damaging DNA, to promote chemotherapy resistance. Current therapeutic approaches exploit the pro-oxidant intracellular environment of malignant B and T lymphoblasts to cause irreversible DNA damage and cell death, however these strategies impact normal haematopoiesis and lead to long lasting side-effects. Therapies suppressing ROS production, especially those targeting ROS producing enzymes such as the NADPH oxidases (NOXs), are emerging alternatives to treat cancers and may be exploited to improve the ALL treatment. Here, we discuss the roles that ROS play in normal haematopoiesis and in ALL. We explore the molecular mechanisms underpinning overproduction of ROS in ALL, and their roles in disease progression and drug resistance. Finally, we examine strategies to target ROS production, with a specific focus on the NOX enzymes, to improve the treatment of ALL.

scholarly journals In vitro Antitumour Activity of Tomato-Extracted Carotenoids on Human Colorectal Carcinoma

2015 ◽  
Vol 43 (2) ◽  
pp. 293-301 ◽  
Author(s):  
Diana CENARIU ◽  
Eva FISCHER-FODOR ◽  
Piroska VIRAG ◽  
Corina TATOMIR ◽  
Mihai CENARIU ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Colon Cancer ◽  
Antioxidant Activity ◽  
Cancer Cell ◽  
Antitumour Activity ◽  
Reactive Oxygen ◽  
Signalling Pathway ◽  
Oxygen Species ◽  
Tnf Receptors

The aim of this research was to establish whether all-trans lycopene extracted from fresh and frozen tomatoes is able to inhibit the in vitro proliferation of colon cancer cells, to trigger apoptosis by reactive oxygen species modulation and to reveal its influence on NF-kβ signalling, through the p65 transcription factor and expression of two TNF receptors: GITR and CD27. The carotenoid extracts containing all-trans lycopene were obtained from fresh (E1) and frozen/thawed (E2) tomatoes (Lycopersicon esculentum Mill.), hybrid ‘Menhir’ F1. DLD-1 and HT-29 human colon adenocarcinoma cell lines were co-cultivated with the two extracts and cytotoxicity, apoptosis, antioxidant activity, reactive oxygen species as well as modulation of NF-kβ signalling pathway were assessed. Tomato extracts E1 and E2 were able to inhibit colon cancer cell growth in vitro. E2 contained a higher proportion of all-trans lycopene and displayed superior cytotoxicity and a better apoptosis inducing capacity. The two extracts proved antioxidant activity against DPPH radicals and were able to scavenge the reactive oxygen species in the treated tumour cells. This study also showed that lycopene acts mainly through p65 protein and moderately by TNF receptors GITR and CD27 to deactivate the NF-kβ signalling pathway involved in cancer cell proliferation.

scholarly journals Involvement of cytosolic phospholipase A2, and the subsequent release of arachidonic acid, in signalling by Rac for the generation of intracellular reactive oxygen species in Rat-2 fibroblasts

2000 ◽  
Vol 348 (3) ◽  
pp. 525-530 ◽  
Author(s):  
Chang-Hoon WOO ◽  
Zee-Won LEE ◽  
Byung-Chul KIM ◽  
Kwon-Soo HA ◽  
Jae-Hong KIM
Keyword(s):  
Reactive Oxygen Species ◽  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Active Form ◽  
Reactive Oxygen ◽  
Cytosolic Phospholipase A2 ◽  
Signalling Pathway ◽  
Oxygen Species ◽  
Cytosolic Phospholipase

Although there have been a number of recent studies on the role of Rac in the generation of reactive oxygen species (ROS), details of the signalling pathway remain unclear. In the present study we analysed the extent to which the activation of cytosolic phospholipase A2 and the resultant release of arachidonic acid (AA) are involved in the Rac-mediated generation of ROS. Transfection of Rat-2 cells with RacV12, a constitutively active form of Rac1, induced elevated levels of ROS, as reflected by increased H2O2-sensitive fluorescence of 2ʹ,7ʹ-dichlorofluorescein. These effects could be blocked by inhibiting phospholipase A2 or 5-lipoxygenase but not by inhibiting cyclo-oxygenase. The application of exogenous AA increased levels of ROS but the effect was dependent on the further metabolism of AA to leukotrienes C4/D4/E4 by 5-lipoxygenase. Indeed, the exogenous application of a mixture of leukotrienes C4/D4/E4 elicited transient elevations in the levels of ROS that were blocked by catalase. These findings indicate that phospholipase A2 and subsequent AA metabolism by 5-lipoxygenase act as downstream mediators in a Rac signalling pathway leading to the generation of ROS.

scholarly journals Role of Calcium/Calcineurin Signalling in Regulating Intracellular Reactive Oxygen Species Homeostasis in Saccharomyces cerevisiae

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1311
Author(s):  
Guohui Li ◽  
Wenxuan Fu ◽  
Yu Deng ◽  
Yunying Zhao
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Intracellular Reactive Oxygen Species ◽  
Signalling Pathway ◽  
Yeast Cells ◽  
Oxygen Species ◽  
Amino Acid Permease ◽  
Intracellular Ros ◽  
High Calcium

The calcium/calcineurin signalling pathway is required for cell survival under various environmental stresses. Using Saccharomyces cerevisiae, we explored the mechanism underlying calcium-regulated homeostasis of intracellular reactive oxygen species (ROS). We found that deletion of acyltransferase Akr1 and C-5 sterol desaturase Erg3 increased the intracellular ROS levels and cell death, and this could be inhibited by the addition of calcium. The hexose transporter Hxt1 and the amino acid permease Agp1 play crucial roles in maintaining intracellular ROS levels, and calcium induced the expression of the HXT1 and AGP1 genes. The cytosolic calcium concentration was decreased in both the akr1Δ and erg3Δ mutants relative to wild-type cells, potentially lowering basal expression of HXT1 and AGP1. Moreover, the calcium/calcineurin signalling pathway also induced the expression of AKR1 and ERG3, indicating that Akr1 and Erg3 might perform functions that help yeast cells to survive under high calcium concentrations. Our results provided mechanistic insight into how calcium regulated intracellular ROS levels in yeast.

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