Radioprotective Potential of Nutraceuticals and their Underlying Mechanism of Action

2021 ◽  
Vol 21 ◽  
Author(s):  
Shabnoor Iqbal ◽  
Muhammad A. Shah ◽  
Azhar Rasul ◽  
Malik Saadullah ◽  
Sobia Tabassum ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Molecular Level ◽  
Underlying Mechanism ◽  
Efficient Treatment ◽  
Current Review ◽  
Genes Expression ◽  
Radiation Induced ◽  
Effects Of Radiation ◽  
Ionizing Radiations ◽  
Anti Inflammation

: Radiations are an efficient treatment modality in cancer therapy. Besides the treatment effects of radiations, the ionizing radiations interact with biological systems and generate reactive oxygen species that interfere with the normal cellular process. Previous investigations of synthetic radioprotectors have shown less effectiveness, mainly owing to some limiting effects. The nutraceuticals act as efficient radioprotectors to protect the tissues from the deleterious effects of radiation. The main radioprotection mechanism of nutraceuticals is the scavenging of free radicals while other strategies are involved modulation of signaling transduction of pathways like MAPK (JNK, ERK1/2, ERK5, and P38), NF-kB, cytokines, and their protein regulatory genes expression. The current review is focused on the radioprotective effects of nutraceuticals including vitamin E, -C, organosulphur compounds, phenylpropanoids, and polysaccharides. These natural entities protect against radiation-induced DNA damage. The review mainly entails the antioxidant perspective and mechanism of action of their radioprotective activities on a molecular level, DNA repair pathway, anti-inflammation, immunomodulatory effects, the effect on cellular signaling pathways, and regeneration of hematopoietic cells.

scholarly journals Curcumin Sensitizes Hepatocellular Carcinoma Cells to Radiation via Suppression of Radiation-Induced NF-κB Activity

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Fei-Ting Hsu ◽  
Yu-Chang Liu ◽  
Tsu-Te Liu ◽  
Jeng-Jong Hwang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Effector Proteins ◽  
Mobility Shift ◽  
Downstream Effector ◽  
Radiation Induced ◽  
Effects Of Radiation ◽  
Hcc Cells

The effects and possible underlying mechanism of curcumin combined with radiation in human hepatocellular carcinoma (HCC) cellsin vitrowere evaluated. The effects of curcumin, radiation, and combination of both on cell viability, apoptosis, NF-κB activation, and expressions of NF-κB downstream effector proteins were investigated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), NF-κB reporter gene, mitochondrial membrane potential (MMP), electrophoretic mobility shift (EMSA), and Western blot assays in Huh7-NF-κB-luc2, Hep3B, and HepG2 cells. Effect of I kappa B alpha mutant (IκBαM) vector, a specific inhibitor of NF-κB activation, on radiation-induced loss of MMP was also evaluated. Results show that curcumin not only significantly enhances radiation-induced cytotoxicity and depletion of MMP but inhibits radiation-induced NF-κB activity and expressions of NF-κB downstream proteins in HCC cells. IκBαM vector also shows similar effects. In conclusion, we suggest that curcumin augments anticancer effects of radiation via the suppression of NF-κB activation.

scholarly journals PTPRD-inactivation-induced CXCL8 promotes angiogenesis and metastasis in gastric cancer and is inhibited by metformin

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Won Jung Bae ◽  
Ji Mi Ahn ◽  
Hye Eun Byeon ◽  
Seokwhi Kim ◽  
Dakeun Lee
Keyword(s):  
Microarray Analysis ◽  
Protein Tyrosine Phosphatase ◽  
Cancer Metastasis ◽  
Tyrosine Phosphatase ◽  
Underlying Mechanism ◽  
Tube Formation ◽  
Potential Therapeutic Target ◽  
Efficient Treatment ◽  
Stat3 Signaling

Abstract Background Protein tyrosine phosphatase receptor delta (PTPRD) is frequently inactivated in various types of cancers. Here, we explored the underlying mechanism of PTPRD-loss-induced cancer metastasis and investigated an efficient treatment option for PTPRD-inactivated gastric cancers (GCs). Methods PTPRD expression was evaluated by immunohistochemistry. Microarray analysis was used to identify differentially expressed genes in PTPRD-inactivated cancer cells. Quantitative reverse transcription (qRT-PCR), western blotting, and/or enzyme-linked immunosorbent assays were used to investigate the PTPRD-CXCL8 axis and the expression of other related genes. An in vitro tube formation assay was performed using HUVECs. The efficacy of metformin was assessed by MTS assay. Results PTPRD was frequently downregulated in GCs and the loss of PTPRD expression was associated with advanced stage, worse overall survival, and a higher risk of distant metastasis. Microarray analysis revealed a significant increase in CXCL8 expression upon loss of PTPRD. This was validated in various GC cell lines using transient and stable PTPRD knockdown. PTPRD-loss-induced angiogenesis was mediated by CXCL8, and the increase in CXCL8 expression was mediated by both ERK and STAT3 signaling. Thus, specific inhibitors targeting ERK or STAT3 abrogated the corresponding signaling nodes and inhibited PTPRD-loss-induced angiogenesis. Additionally, metformin was found to efficiently inhibit PTPRD-loss-induced angiogenesis, decrease cell viability in PTPRD-inactivated cancers, and reverse the decrease in PTPRD expression. Conclusions Thus, the PTPRD-CXCL8 axis may serve as a potential therapeutic target, particularly for the suppression of metastasis in PTPRD-inactivated GCs. Hence, we propose that the therapeutic efficacy of metformin in PTPRD-inactivated cancers should be further investigated.

scholarly journals Upregulation of miR-150-5p alleviates LPS-induced inflammatory response and apoptosis of RAW264.7 macrophages by targeting Notch1

2020 ◽  
Vol 15 (1) ◽  
pp. 544-552
Author(s):  
Xiaoyan Deng ◽  
Zhixing Lin ◽  
Chao Zuo ◽  
Yanjie Fu
Keyword(s):  
Inflammatory Response ◽  
Underlying Mechanism ◽  
Notch Receptor ◽  
Raw264.7 Cells ◽  
Luciferase Reporter ◽  
Raw264.7 Macrophages ◽  
Factor Α ◽  
Anti Inflammation ◽  
Necrosis Factor ◽  
Dual Luciferase Reporter Assay

AbstractCirculating miR-150-5p has been identified as a prognostic marker in patients with critical illness and sepsis. Herein, we aimed to further explore the role and underlying mechanism of miR-150-5p in sepsis. Quantitative real-time-PCR assay was performed to detect the expression of miR-150-5p upon stimulation with lipopolysaccharide (LPS) in RAW264.7 cells. The levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were measured by ELISA assay. Cell apoptosis was determined using flow cytometry. Western blot was used to assess notch receptor 1 (Notch1) expression in LPS-induced RAW264.7 cells. Dual-luciferase reporter assay was employed to validate the target of miR-150-5p. Our data showed that miR-150-5p was downregulated and Notch1 was upregulated in LPS-stimulated RAW264.7 cells. miR-150-5p overexpression or Notch1 silencing alleviated LPS-induced inflammatory response and apoptosis in RAW264.7 cells. Moreover, Notch1 was a direct target of miR-150-5p. Notch1 abated miR-150-5p-mediated anti-inflammation and anti-apoptosis in LPS-induced RAW264.7 cells. miR-150-5p alleviated LPS-induced inflammatory response and apoptosis at least partly by targeting Notch1 in RAW264.7 cells, highlighting miR-150-5p as a target in the development of anti-inflammation and anti-apoptosis drugs for sepsis treatment.

scholarly journals Inhibition of NMDA receptors by agmatine is followed by GABA/glutamate balance in benzodiazepine withdrawal syndrome

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Hira Rafi ◽  
Hamna Rafiq ◽  
Muhammad Farhan
Keyword(s):  
Mechanism Of Action ◽  
Withdrawal Syndrome ◽  
Substance Dependence ◽  
Screen Test ◽  
Underlying Mechanism ◽  
Depressive Mood ◽  
Elevated Plus Maze Test ◽  
Plus Maze ◽  
Compulsive Behaviors ◽  
Benzodiazepine Withdrawal

Abstract Background Drug withdrawal syndrome occurs due to abrupt cessation of an addictive substance. Dependence to diazepam can be manifested by withdrawal syndrome which may include symptoms such as irritability, psychosis, sleep disturbance, seizures, mood disturbance, and anxiety. Studies have described the therapeutic role of agmatine in various neurological disorders such as depressive mood, learning deficits, anxiety, memory impairment, and psychosis. Various studies have also validated agmatine as a putant neuromodulator and revealed its mechanism of action with other neurotransmitters. The study was designed to reveal the potentials of agmatine in benzodiazepine withdrawal syndrome by maintaining GABA/glutamate balance. The study aimed to determine the underlying mechanism of action of agmatine at synaptic level using behavioral and biochemical evaluations. Results Agmatine significantly enhanced locomotion in open filed test and decreased anxiety as observed in elevated plus maze test (p < 0.01). Agmatine also reduced withdrawal symptoms scores along with compulsive behaviors in marble burying test and improved muscular strength by decreasing latency to fall in inverted screen test (p < 0.01). Moreover, agmatine established GABA/glutamate balance by increasing GABA levels and decreased glutamate concentration significantly (p < 0.01). Conclusion The present study reveals the possible mechanism of action of agmatine on NMDA receptor at GABA interneurons and glutamate post synaptic neuron that may lead to GABA/glutamate balance during withdrawal syndrome.

scholarly journals A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junko Okano ◽  
Yuki Nakae ◽  
Takahiko Nakagawa ◽  
Miwako Katagi ◽  
Tomoya Terashima ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Underlying Mechanism ◽  
Basal Cells ◽  
Barrier Dysfunction ◽  
Skin Injury ◽  
Accelerated Proliferation ◽  
Radiation Induced ◽  
Bone Marrow Derived Cells ◽  
Injury Recovery

AbstractExposure to moderate doses of ionizing radiation (IR), which is sufficient for causing skin injury, can occur during radiation therapy as well as in radiation accidents. Radiation-induced skin injury occasionally recovers, although its underlying mechanism remains unclear. Moderate-dose IR is frequently utilized for bone marrow transplantation in mice; therefore, this mouse model can help understand the mechanism. We had previously reported that bone marrow-derived cells (BMDCs) migrate to the epidermis-dermis junction in response to IR, although their role remains unknown. Here, we investigated the role of BMDCs in radiation-induced skin injury in BMT mice and observed that BMDCs contributed to skin recovery after IR-induced barrier dysfunction. One of the important mechanisms involved the action of CCL17 secreted by BMDCs on irradiated basal cells, leading to accelerated proliferation and recovery of apoptosis caused by IR. Our findings suggest that BMDCs are key players in IR-induced skin injury recovery.

Oral Sequelae of Head and Neck Radiotherapy

2003 ◽  
Vol 14 (3) ◽  
pp. 199-212 ◽  
Author(s):  
A. Vissink ◽  
J. Jansma ◽  
F.K.L. Spijkervet ◽  
F.R. Burlage ◽  
R.P. Coppes
Keyword(s):  
Head And Neck ◽  
Neck Region ◽  
Normal Tissues ◽  
Radiation Caries ◽  
Temporomandibular Joints ◽  
Clinical Consequences ◽  
Radiation Induced ◽  
Heavy Burden ◽  
Effects Of Radiation ◽  
Induced Changes

In addition to anti-tumor effects, ionizing radiation causes damage in normal tissues located in the radiation portals. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on, e.g., salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. The clinical consequences of radiotherapy include mucositis, hyposalivation, taste loss, osteoradionecrosis, radiation caries, and trismus. Mucositis and taste loss are reversible consequences that usually subside early post-irradiation, while hyposalivation is normally irreversible. Furthermore, the risk of developing radiation caries and osteoradionecrosis is a life-long threat. All these consequences form a heavy burden for the patients and have a tremendous impact on their quality of life during and after radiotherapy. In this review, the radiation-induced changes in healthy oral tissues and the resulting clinical consequences are discussed.

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