In vitro studies on radioprotective efficacy of silymarin against γ-irradiation

Adhikari, Manish; Dhaker, Atlar Singh; Adhikari, Jawahar Singh; Иванов, Веселин; Singh, Vijay K.; Chawla, Raman; Kumar, Raj; Sharma, Rakesh Kumar; Karamalakova, Yanka; Gadjeva, V.; Arora, Rajesh

doi:10.3109/09553002.2013.741285

Cited by 24 publications

(14 citation statements)

References 42 publications

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“…The intracellular reactive oxygen species (ROS) generation was determined by flowcytometry using CM-H 2 DCFDA [27], [35], [36]. Briefly, cells were harvested following different treatments and incubated with CM-H 2 DCFDA (20 µM) to determine free radical-mediated oxidation of dye at room temperature in dark condition.…”

Section: Methodsmentioning

confidence: 99%

“…The changes in cell cycle phase distribution were measured flowcytometrically by using PI as previously described by Adhikari et al [27], [35]. Briefly, cells (1×10 6 cells/sample) were harvested and fixed in 70% ice cold ethanol.…”

Section: Methodsmentioning

confidence: 99%

“…The damage to DNA was measured using single cell gel electrophoresis (comet assay) as previously described [35], [37], [38]. In brief, single cell suspensions were prepared andsuspended in low-melting point agarose (0.8%) in phosphate buffer saline (pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

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Surface Levels of CD20 Determine Anti-CD20 Antibodies Mediated Cell Death In Vitro

et al. 2014

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BackgroundThe sensitivity of human Burkitt's lymphoma cells to rituximab (Rtx) and tositumomab (Tst) was assessed on cells expressing different levels of CD20 on surface. Cells that harbor low CD20 levels may resists against therapeutics response to CD20-specific antibodies. We postulated that, radiation-induced modulation of CD20 surface levels may play a crucial and central role in determining the relative efficacy of rituximab and tositumomab in treating Burkitt's lymphoma disease. Here, we examined the γ-radiation-induced CD20 expression in the Burkitt lymphoma cell line ‘Daudi’ and the relation of differential levels of CD20 with anti-CD20 mAbs mediated cell death.MethodologyIn this study we examined kinetics of CD20 expression following sub lethal doses ofγ-radiation to Daudi cells and thereafter anti-CD20 mAbs (rituximab and tositumomab) were added in cell suspensions. The correlation of kinetics of CD20 expression and cells treated with anti-CD20 mAbs/or corresponding isotype Abs with special reference to changes in mitochondrial membrane potential and reactive oxygen species generation was also examined. Further, we also investigated the efficacy of anti-CD20 mAbs and possible induction of cell death in relation to levels of CD20 cell surface expression.ConclusionThis report provides evidence that CD20 expression can be induced by exposure of cells to γ-radiation. In addition, these findings demonstrated that the efficacy of anti-CD20 mAbs is dependent on the surface levels of CD20. Based on these findings, we hypothesized (i) irradiation just prior to immunotherapy may provide new treatment options even in aggressive B cell tumors, which are resistant to current therapies in vivo (ii) The efficacy of induction of apoptosis varies with type of monoclonal antibodies in vitro.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Surface Levels of CD20 Determine Anti-CD20 Antibodies Mediated Cell Death In Vitro

et al. 2014

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“…Approximately 95 percent of colorectal cancers are adenocarcinomas. Silymarin has already been evidentiated for its radioprotective efficacy both at in vitro and in vivo levels [2][3][4][5] . The anticancer effects of silymarin can be understood by various molecular mechanisms including blocking of carcinogenesis at different stages, such as initiation, promotion, and progression.…”

Section: Introductionmentioning

confidence: 99%

Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells

Lal

Gupta

2016

Discoveries (Craiova)

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Recent reports demonstrated the role of silymarin as a cytoprotective agent for normal cells against ionizing or non-ionizing (UV) radiation, and in inhibiting the chemically initiated or promoted carcinogenesis in several malignancies, such as skin or prostate cancers. Silymarin is a plant flavonoid obtained from milk thistle; the main active principles in milk thistle are silybin (silibinin), sylichrisitin and silydianin, commonly referred as silymarin. In the present study, we aimed to investigate the radiation modulatory effects of silymarin on cancer cells. For this, we used the HCT-15 and RKO colon cancer cell lines as a model. Pre-irradiation treatment of cells with silymarin (20 µg/ml) followed by radiation exposure inhibits colon cancer cell proliferation and enhances cell death in a time-dependent manner. We have also examined the changes in p53 phosphorylation at Ser15, phosphorylation of p38 and their association with DNA damage. Silymarin was found to reduce proliferation of the human colon carcinoma cells in a concentration and timedependent manner. Moreover, percentage of cell death was also increased in combined treatment (20µg/ml of silymarin + radiation). Our studies indicate that the combination increases the arrest of cells in G 2 /M phase of cell cycle, DNA damageinduced decrease in mitochondrial membrane potential (MMP) and a decrease of the reactive oxygen species (ROS) levels, which are associated with an increase in cell death. Altogether, these results suggest that silymarin sensitizes colon cancer cells to radiation, strategy with potential for colon cancer treatment. Noteworthy, since silymarin was previously shown to confer protection against radiation in at least some types of normal tissues, additional studies are needed to further investigate the potential of silymarin in colon cancer therapy when combined with radiation, its potential protective effects on normal tissues and its mechanisms of action.

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“…Gaertn., also commonly known as Milk thistle or St. Mary's thistle, is well known for its antioxidant and chemoprotectant effects on liver. The antioxidative property of flavonoids present in Silybum marianum has been reported to be dependent on availability of metal ions in cellular milieu (Adhikari et al, 2010(Adhikari et al, , 2013. It is readily absorbed after oral ingestion and has a strong first-pass effect through the liver (Burczynski et al, 2012;Adhikari et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity

Adhikari

Arora

2014

Environ. Toxicol.

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The main focus of this study is evaluation of radioprotective efficacy of silymarin, a flavonolignan, against γ-radiation-induced damage to hematological, vital organs (liver and intestine), and immune system. Survival studies revealed that silymarin (administered orally for 3 days) provided maximum protection (67%) at 70 mg/kg body weight (b.wt.) against lethal 9 Gy γ-irradiation (dose reduction factor = 1.27). The study revealed significant (p < 0.05) changes in levels of catalase (12.57 ± 2.58 to 30.24 ± 4.89 units), glutathione peroxidase (6.23 ± 2.95 to 13.26 ± 1.36 µg of reduced glutathione consumed/min/mg protein), glutathione reductase (0.25 ± 5.6 to 11.65 ± 2.83 pM NADPH consumed/min/mg protein), and superoxide dismutase (11.74 ± 0.2 to 16.09 ± 3.47 SOD U/mg of protein) activity at 30th day. Silymarin pretreated irradiated group exhibited increased proliferation in erythrocyte count (1.76 ± 0.41 × 10(6) to 9.25 ± 0.24 × 10(6) ), hemoglobin (2.15 ± 0.48g/dL to 14.77 ± 0.25g/dL), hematocrit (4.55 ± 0.24% to 37.22 ± 0.21%), and total leucocyte count (1.4 ± 0.15 × 10(6) to 8.31 ± 0.47 × 10(6) ) as compared with radiation control group on 15th day. An increase in CD4:CD8 ratio was witnessed (0.2-1%) at 30th day time interval using flow cytometry. Silymarin also countered radiation-induced decrease (p < 0.05) in regulatory T-cells (Tregs ) (11.23% in radiation group at 7th day versus 0.1% in pretreated silymarin irradiated group at 15th day). The results of this study indicate that flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity and might prove useful in management of nuclear and radiological emergencies. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 641-654, 2016.

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In vitro studies on radioprotective efficacy of silymarin against γ-irradiation

Abstract: Protection against radiation-induced cell-death and DNA damage by silymarin could be attributed to a reduction in ROS induced by γ-radiation. In vitro experiments on HEK cells explicitly prove that silymarin is a promising, effective and safe radiation countermeasure agent.

Cited by 24 publications

References 42 publications

Surface Levels of CD20 Determine Anti-CD20 Antibodies Mediated Cell Death In Vitro

Surface Levels of CD20 Determine Anti-CD20 Antibodies Mediated Cell Death In Vitro

Studies on radiation sensitization efficacy by silymarin in colon carcinoma cells

The flavonolignan-silymarin protects enzymatic, hematological, and immune system against γ-radiation-induced toxicity

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