Cytokine and inflammatory mediators are associated with cytotoxic, anti-inflammatory and apoptotic activity of honeybee venom

AbstractObjectiveThe present study aimed to evaluate cytotoxic, apoptotic, and anti-inflammatory properties of bee venom (BV) as well as changes in cytokine secretion levels and nitric oxide (NO) production using three different cancer cell lines [liver (Hep-G2), breast (MCF-7), and cervical (HPV-18 infected HeLa cells)] and two normal cells (splenocytes and macrophages (MQ).MethodsCytotoxic activity of BV against tumor cell lines and normal splenocytes/MQ was tested by MTT assay. By ELISA (ELISA); Tumor necrosis factor (TNF-α), Interleukine (IL-10) and interferon (IFN-γ) were measured. Caspase three expressions was evaluated using reverse transcription-polymerase chain reaction (RT-PCR). Nitric oxide (NO) was estimated using a colorimetric assay.ResultsBV has a significant cytotoxic effect on all cell lines in a dose- and time-dependent manner; none of them was toxic for normal cells. Treating Hep-G2 cells with BV showed a reduction in IL-10, elevation in TNF-α with no change in IFN-γ level. MCF-7 cells have low IL-10 and TNF-α and high IFN-γ production level. Elevation of IL-10 and IFN-γ coincides with a reduction in TNF-α level was demonstrated in HeLa cells. The expression of Caspase three was dramatically increased with elevation in BV concentration in all tested cancer cell lines. A gradual decrease in NO production by MQ with increasing BV dose was observed.ConclusionTaken together, our results stressed on the importance of BV as a potent anti-tumor agent against various types of cancers (Liver, Breast, and Cervix). Further steps towards the use of BV for pharmacological purposes must be done.

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Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages

Scientific Reports ◽

10.1038/s41598-020-80804-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Haidy A. Saleh ◽

Eman Ramdan ◽

Mohey M. Elmazar ◽

Hassan M. E. Azzazy ◽

Anwar Abdelnaser

Keyword(s):

Nitric Oxide ◽

Inflammatory Response ◽

Raw 264.7 Cells ◽

Inos Mrna ◽

No Production ◽

Raw 264.7 ◽

Mrna Levels ◽

Protective Effects ◽

Tnf Α ◽

Ifn Γ

AbstractDoxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

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Nitric oxide interacts with cholinoceptors to modulate insulin secretion by pancreatic β cells

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-020-02443-9 ◽

2020 ◽

Vol 472 (10) ◽

pp. 1469-1480

Author(s):

Bashair M. Mussa ◽

Ankita Srivastava ◽

Abdul Khader Mohammed ◽

Anthony J. M. Verberne

Keyword(s):

Nitric Oxide ◽

Insulin Secretion ◽

Cell Viability ◽

Combined Treatment ◽

No Production ◽

Β Cells ◽

Β Cell ◽

Pancreatic Β Cells ◽

Tnf Α ◽

Ifn Γ

Abstract Dysfunction of the pancreatic β cells leads to several chronic disorders including diabetes mellitus. Several mediators and mechanisms are known to be involved in the regulation of β cell secretory function. In this study, we propose that cytokine-induced nitric oxide (NO) production interacts with cholinergic mechanisms to modulate insulin secretion from pancreatic β cells. Using a rat insulinoma cell line INS-1, we demonstrated that β cell viability decreases significantly in the presence of SNAP (NO donor) in a concentration- and time-dependent manner. Cell viability was also found to be decreased in the presence of a combined treatment of SNAP with SMN (muscarinic receptor antagonist). We then investigated the impact of these findings on insulin secretion and found a significant reduction in glucose uptake by INS-1 cells in the presence of SNAP and SMN as compared with control. Nitric oxide synthase 3 gene expression was found to be significantly reduced in response to combined treatment with SNAP and SMN suggesting an interaction between the cholinergic and nitrergic systems. The analysis of gene and protein expression further pin-pointed the involvement of M3 muscarinic receptors in the cholinergic pathway. Upon treatment with cytokines, reduced cell viability was observed in the presence of TNF-α and IFN-γ. A significant reduction in insulin secretion was also noted after treatment with TNF-α and IFN-γ and IL1-β. The findings of the present study have shown for the first time that the inhibition of the excitatory effects of cholinergic pathways on glucose-induced insulin secretion may cause β cell injury and dysfunction of insulin secretion in response to cytokine-induced NO production.

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Novel thalidomide analogs: Anti-angiogenic and apoptotic effects on Hep-G2 and MCF-7 cancer cell lines

Biomedicine & Aging Pathology ◽

10.1016/j.biomag.2014.03.002 ◽

2014 ◽

Vol 4 (3) ◽

pp. 179-189 ◽

Cited By ~ 6

Author(s):

Roba Talaat ◽

Waheba El-Sayed ◽

Hussein Agwa ◽

Amira Gamal-Eldeen ◽

Shaden Moawia ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Hep G2 ◽

Apoptotic Effects ◽

Mcf 7

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Biological Effect of Organically Coated Grias neuberthii and Persea americana Silver Nanoparticles on HeLa and MCF-7 Cancer Cell Lines

Journal of Nanotechnology ◽

10.1155/2018/9689131 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Lizeth Salazar ◽

María José Vallejo López ◽

Marcelo Grijalva ◽

Luis Castillo ◽

Alexander Maldonado

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Cell Viability ◽

Cell Lines ◽

Cancer Cell ◽

Hela Cells ◽

Biological Effect ◽

Persea Americana ◽

Expression Levels ◽

Mcf 7

The aim of this study was to assess the biological effect of organically coated Grias neuberthii (piton) fruit and Persea americana (avocado) leaves nanoparticles (NPs) on cervical cancer (HeLa) and breast adenocarcinoma (MCF-7) cells with an emphasis on gene expression (p53 transcription factor and glutathione-S-transferase GST) and cell viability. UV-Vis spectroscopy analysis showed that synthesized AgNPs remained partially stable under cell culture conditions. HeLa cells remained viable when exposed to piton and avocado AgNPs. A statistically significant, dose-dependent cytotoxic response to both AgNPs was found on the breast cancer (MCF-7) cell line at concentrations above 50 µM. While expression levels of transcription factor p53 showed downregulation in treated MCF-7 and HeLa cells, GST expression was not affected in both cell lines treated. Cell viability assays along with gene expression levels in treated MCF-7 cells support a cancer cell population undergoing cell cycle arrest. The selective toxicity of biosynthesized piton/avocado AgNPs on MCF-7 cells might be of value for novel therapeutics.

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In Vitro Evaluation of Cytotoxic Activities of Marketed Herbal Products in Ghana

Journal of Evidence-Based Integrative Medicine ◽

10.1177/2515690x18790723 ◽

2018 ◽

Vol 23 ◽

pp. 2515690X1879072 ◽

Cited By ~ 2

Author(s):

Sylvester Languon ◽

Isaac Tuffour ◽

Emmanuel Ekow Quayson ◽

Regina Appiah-Opong ◽

Osbourne Quaye

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Jurkat Cells ◽

Total Phenolic ◽

Cytotoxic Activities ◽

Hep G2 ◽

Herbal Products ◽

Mcf 7

There are numerous herbal products on the Ghanaian market that are purported to cure various ailments, including cancer. However, scientific investigations on efficacy and toxicity of most of these products are not done. The aim of the study was to assess the anticancer potentials of herbal products on the Ghanaian market. Antiproliferative effects of Kantinka BA (K-BA), Kantinka Herbaltics (K-HER), Centre of Awareness (COA), a stomach (STO) and multicancer (MUT) product were evaluated in vitro using liver (Hep G2), breast (MCF-7), prostate (PC-3 and LNCaP), and blood (Jurkat) cancer cell lines. Cytotoxicity of the medicinal products was assessed using tetrazolium-based colorimetric assay, and total phenolic content and antioxidant activity of the products were determined using Folin-Ciocalteau and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, respectively. Phytochemical screening resulted in the detection of terpenoids and flavonoids in most of the products, and alkaloids were detected in only MUT. Tannins were absent from all the products. The highest and lowest concentrations of phenolics were recorded for MUT and K-BA, respectively. The highest and lowest antioxidant activities were measured for MUT and K-HER, respectively. Only 2 products (STO and MUT) were cytotoxic to Hep G2 cells; with MUT being the only product that was cytotoxic to MCF-7 cells. All but K-BA were cytotoxic to PC-3 cells, while all products except K-HER were cytotoxic to LNCaP and Jurkat cells. The study thus confirms that the herbal products have selective cytotoxic activities against the tested cancer cell lines. However, comprehensive toxicity studies must be conducted to establish their safety.

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Macrophages Promote Oxidative Metabolism To Drive Nitric Oxide Generation in Response to Trypanosoma cruzi

Infection and Immunity ◽

10.1128/iai.00809-16 ◽

2016 ◽

Vol 84 (12) ◽

pp. 3527-3541 ◽

Cited By ~ 23

Author(s):

Sue-jie Koo ◽

Imran H. Chowdhury ◽

Bartosz Szczesny ◽

Xianxiu Wan ◽

Nisha J. Garg

Keyword(s):

Gene Expression ◽

Nitric Oxide ◽

Trypanosoma Cruzi ◽

Oxidative Metabolism ◽

Cytokine Profile ◽

No Production ◽

Metabolic State ◽

Content Type ◽

Tnf Α ◽

Ifn Γ

Trypanosoma cruziis the causative agent of chronic chagasic cardiomyopathy. Why macrophages (mφs), the early responders to infection, fail to achieve parasite clearance is not known. Mouse (RAW 264.7) and human (THP-1 and primary) mφs were infected for 3 h and 18 h withT. cruziTcI isolates, SylvioX10/4 (SYL, virulent) and TCC (nonpathogenic), which represent mφ stimulation and infection states, respectively. Mφs incubated with lipopolysaccharide and gamma interferon (LPS/IFN-γ) and with interleukin-4 (IL-4) were used as controls. We monitored the cytokine profile (using enzyme-linked immunosorbent assay [ELISA]), reactive oxygen species (ROS; fluorescent probes), nitric oxide (·NO; Griess assay), and metabolic state using a custom-designed mitoxosome array and Seahorse XF24 Analyzer. LPS/IFN-γ treatment of mφs elicited a potent increase in production of tumor necrosis alpha (TNF-α) at 3 h and of ROS and ·NO by 18 h. Upon SYL infection, murine mφs elicited an inflammatory cytokine profile (TNF-α ≫ TGF-β + IL-10) and low levels of ·NO and ROS production. LPS/IFN-γ treatment resulted in the inhibition of oxidative metabolism at the gene expression and functional levels and a switch to the glycolytic pathway in mφs, while IL-4-treated mφs utilized oxidative metabolism to meet energy demands. SYL infection resulted in an intermediate functional metabolic state with increased mitoxosome gene expression and glycolysis, and IFN-γ addition shut down the oxidative metabolism in SYL-infected mφs. Further, TCC- and SYL-stimulated mφs exhibited similar levels of cell proliferation and production of TNF-α and ROS, while TCC-stimulated mφs exhibited up to 2-fold-higher levels of oxidative metabolism and ·NO production than SYL-infected mφs. Inhibiting ATP-coupled O2consumption suppressed the ·NO generation in SYL-infected mφs. Mitochondrial oxygen consumption constitutes a mechanism for stimulating ·NO production in mφs duringT. cruziinfection. Enhancing the oxidative metabolism provides an opportunity for increased ·NO production and pathogen clearance by mφs to limit disease progression.

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Protective Role of Nitric Oxide inStaphylococcus aureus Infection in Mice

Infection and Immunity ◽

10.1128/iai.66.3.1017-1022.1998 ◽

1998 ◽

Vol 66 (3) ◽

pp. 1017-1022 ◽

Cited By ~ 65

Author(s):

Sanae Sasaki ◽

Tomisato Miura ◽

Shinsuke Nishikawa ◽

Kyogo Yamada ◽

Mayuko Hirasue ◽

...

Keyword(s):

Nitric Oxide ◽

Spleen Cell ◽

Cell Cultures ◽

Protective Role ◽

Inos Mrna ◽

No Production ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Ifn Γ

ABSTRACT This study was carried out to determine the role of nitric oxide (NO) in Staphylococcus aureus infection in mice. NO production in spleen cell cultures was induced by heat-killed S. aureus. Expression of mRNA of the inducible isoform of NO synthase (iNOS) was induced in the spleens and kidneys of S. aureus-infected mice. When mice were treated with monoclonal antibodies (MAbs) against tumor necrosis factor alpha (TNF-α) or gamma interferon (IFN-γ) before S. aureus infection, the induction of iNOS mRNA expression in the kidneys was inhibited. These MAbs also inhibited NO production in spleen cell cultures stimulated with heat-killed S. aureus. NO production in the spleen cell cultures and levels of urinary nitrate plus nitrite were suppressed by treatment with aminoguanidine (AG), a selective inhibitor of iNOS. The survival rates of AG-treated mice were significantly decreased by either lethal or sublethal S. aureusinfections. However, an effect of AG administration on bacterial growth was not observed in the spleens and kidneys of mice during either type of infection. Production of TNF-α and IFN-γ was not affected by AG treatment in vitro and in vivo. These results suggest that NO plays an important role in protection from lethality by the infection, but the protective role of NO in host resistance against S. aureusinfection was not proved. Moreover, our results show that TNF-α and IFN-γ regulate NO production while NO may not be involved in the regulation of the production of these cytokines during S. aureus infection.

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Isolation and Evaluation of Bioactive Compounds from Rheum emodi and their Anti-Inflammatory and Anticancer Properties

International Journal of Agriculture and Biology ◽

10.17957/ijab/15.1777 ◽

2021 ◽

Vol 25 (06) ◽

pp. 1161-1172

Author(s):

Sang Koo Park

Keyword(s):

Ethyl Acetate ◽

Cell Lines ◽

Cancer Cell ◽

Ethyl Acetate Extract ◽

Cancer Cell Lines ◽

Flavonoid Compound ◽

Dependent Manner ◽

Tnf Α ◽

Anti Inflammatory ◽

Mcf 7

Rheum emodi Wall. ex Meissn is a popular medicinal herb having wide application in traditional medicine for treating of several diseases. The present study was aimed to identify and isolate phytochemicals present in ethyl acetate extract fraction of R. emodi and to evaluate the anticancer and anti-inflammatory activities of water/organic solvent fractions and isolated compounds of R. emodi rhizome extracts. Based on the structure, flavonoid compound i.e., Myricitrin (sym. Myricetin 3- rhamnoside), myricetin 3-galloylrhamnoside and myricetin were identified to be present in ethyl acetate extract. The molecular weight of compound 1 cannot be identified; while compound 5 remained unknown as there was not enough evidence to propose its structure. The isolated compounds and different solvent fractions were tested for their anticancer and antiinflammatory activities. Among Myricetins derivatives, particularly unknown compounds significantly induced the apoptosis and restrained the proliferation of cancer cell lines (A549 and MCF-7) and inhibited the LPS induced NO production (proinflammatory mediator), IL-6 activity, IL-1β and TNF-α (cytokines) activity in RAW 264.7 macrophages in a dose dependent manner and was effective even at lower concentration (50 µg/mL). Similarly, the higher concentration of aqueous and solvent fractions exhibited strong cytotoxic and anti-inflammatory activities. However, water and dichloromethane fractions were most effective in inhibiting the anticancer activities in A549 and MCF-7 cancer cell lines, respectively. At lower concentration (50 and 100 µg/mL), highest inhibition activity for NO, IL-6 and IL-1β was noted with ethyl acetate fractions and n-Hexane fractions; while water and n-Butanol (fractions) strongly inhibited the TNF-α activity at lower (100 µg/mL) and high (200 µg/mL) concentration, respectively. In conclusion, the isolated compounds from R. emodi rhizome extracts and its rhizome solvent fractions exhibit strong anti-cancer and anti-inflammatory activities and can be used to develop chemotherapeutics and anti-inflammation drugs. © 2021 Friends Science Publishers

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Study on Chemical Constituents and Cytotoxic Activities of Salacia chinensis Growing in Vietnam

Zeitschrift für Naturforschung B ◽

10.1515/znb-2010-1017 ◽

2010 ◽

Vol 65 (10) ◽

pp. 1284-1288 ◽

Cited By ~ 7

Author(s):

Tran Thi Minh ◽

Nguyen Thi Hoang Anh ◽

Vu Dao Thang ◽

Tran Van Sung

Keyword(s):

Spectral Analysis ◽

Ethyl Acetate ◽

Cell Lines ◽

Cancer Cell ◽

Ethyl Acetate Extract ◽

Chemical Constituents ◽

Cytotoxic Activities ◽

Good Activity ◽

Hep G2 ◽

Mcf 7

Two new triterpenoids, named 7α,21α-dihydroxyfriedelane-3-one (1) and 7α,29-dihydroxyfriedelane- 3-one (2) have been isolated from the ethyl acetate extract of the stems of Salacia chinensis besides the known triterpenoid 21α,30-dihydroxyfriedelane-3-one (3). The structures of the isolated compounds were elucidated on the basis of spectral analysis. Eight triterpenoids from this plant have been tested against the four cancer cell lines Hep-G2, LU, KB, and MCF-7. The new compound 1 showed good activity against all four tested cell lines.

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