scholarly journals Immunologic Effect of Polysaccharides Extracted from Sipunculus nudus (SNP) on Hepatoma HepG2-bearing Mice

2017 ◽  
Author(s):  
Jie Su ◽  
Linlin Jiang ◽  
Jingna Wu ◽  
Zhiyu Liu ◽  
Yuping Wu
Keyword(s):  
Antitumor Agent ◽  
Inhibitory Effect ◽  
Water Soluble ◽  
Antitumor Effects ◽  
Sipunculus Nudus ◽  
Immunological Effect ◽  
Tnf Α ◽  
Immunologic Effect ◽  
Summary Statement ◽  
Hepatoma Hepg2

AbstractSince many studies have clarified the biological activity of polysaccharides, we investigated the effect of SNP which was the water-soluble polysaccharides extracted from Sipunculus nudus on Hepatoma HepG2-bearing Mice to verify the potential of SNP as an effective clinical agent for liver cancer therapy. SNP were administered at the doses of 50,100, and 200 mg/kg to HepG2-bearing mice to determine their antitumor effects. SNP had an inhibitory effect on the growth of HepG2 cells and enhanced the immunological effect on HepG2 tumor-bearing mice. SNP increased the expression of IL-2, IFN-γ, and TNF-α cytokines in serum, suggesting that SNP can strengthen the antitumor immune response. In addition, SNP increased ATF4, DDIT3, and IkBα expression and decreased CYR61, HSP90, and VEGF expression, all of which are proteins involved in antitumor activity and cell death/survival. our results suggested that SNP may be a novel antitumor agent.Summary statementSNP(polysaccharides extracted from Sipunculus nudus) mediates anti-tumor activity through influencing immunoregulation, and SNP can be explored as a promising candidate for future anticancer drug.

Inhibitory Effect of Water‐Soluble Chitosan on TNF‐α and IL‐8 Secretion from HMC‐1 Cells

2004 ◽  
Vol 26 (3) ◽  
pp. 401-409 ◽  
Author(s):  
Mi‐Sun Kim ◽  
Hyun Ja You ◽  
Mi Kyung You ◽  
Nam‐Song Kim ◽  
Bum Sang Shim ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Water Soluble ◽  
Effect Of Water ◽  
Tnf Α

Mechanism of Immune System Activation by (1,4)-α-D-glucan Isolated from Tinospora cordifolia in Macrophages.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3833-3833
Author(s):  
P.K. Raveendran Nair ◽  
Steven J. Melnick ◽  
Ziad A. Khatib ◽  
Reshma Ramachandran ◽  
Enrique A. Escalon ◽  
...  
Keyword(s):  
Immune System ◽  
Inhibitory Effect ◽  
Water Soluble ◽  
Hek293 Cells ◽  
Tinospora Cordifolia ◽  
Dependent Manner ◽  
The Novel ◽  
Zymosan A ◽  
Tnf Α ◽  
Dose Dependent

Abstract We have characterized and reported the immunostimulating properties of a novel polysaccharide - (1,4)-α-D-glucan (RR1)- isolated from the medicinal plant Tinospora cordifolia [23]. This novel glucan is water soluble and having (1, 4)-α-D-glycosidic linkages in the main chain and (1, 6)-α-D-glycosidic linked side chains at an interval of 6, 7 glucose units. The signaling mechanism of the novel (1,4)-a-D-glucan (RR1) was investigated in macrophages to evaluate its immunostimulating properties. When RAW264.7 macrophages were incubated with RR1 at 4°C, the novel glucan inhibited the phagocytosis of unopsonized zymosan A bioparticles in a dose-dependent manner. RR1 also inhibited the binding and internalization of opsonized zymosan A bioparticles, although at a lower level than laminarin. Incubation of macrophages with anti-CD11b mAb followed by RR1 failed to show any inhibitory effect on RR1-induced TNF-α synthesis confirming that complement receptor 3 (CR3) is not involved in the opsonic binding and internalization of RR1 in macrophages unlike zymosan A. The anti-CD11b mAb has significant inhibitory effect on the zymosan A-induced tumor necrosis factor (TNF)-α synthesis. RR1 induced TNF-α synthesis in macrophages in a dose-dependent manner which can be completely inhibited by the NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or curcumin. RR1 activated NF-κB in a time- and dose-dependent manner and this modulation of nuclear NF-κB activity is associated with the degradation of I-κB a thus facilitating the translocation of NF-κB into the nucleus. RR1-induced NF-κB activity peaks at 8 h of RR1 stimulation while I-κB a degradation occurred within 1 h of stimulation. RR1-induced NF-κB activation occurred through TLR6 signaling as evidenced by the synthesis of IL-8 in TLR6-transfected HEK293 cells. These results show that the novel (1,4)-α-D glucan from Tinospora cordifolia activates the immune system through the activation of macrophages that occurs through TLR6 signaling, NF-κB translocation and cytokine production. (Supported by Miami Children’s Hospital Foundation research funds).

scholarly journals The Inhibitory Effect of 3β-Hydroxy-12-oleanen-27-oic Acid on Growth and Motility of Human Hepatoma HepG2 Cells through JNK and Akt Signaling Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Juanjuan Wang ◽  
Xiangfeng Chen ◽  
Zhihua Zhou ◽  
Jinhui Li ◽  
Hongxiang Sun
Keyword(s):  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
Pcr Array ◽  
Human Hepatoma ◽  
Antitumor Effects ◽  
Human Hepatoma Hepg2 Cells ◽  
Hepatoma Hepg2

3β-Hydroxy-12-oleanen-27-oic acid (ATA) was a main antitumor active triterpene from the rhizomes ofAstilbe chinensis. In this study, we investigated its effects on growth, apoptosis, cell cycle, motility/invasion, and metatasis in human hepatoma HepG2 cellsin vitroand antimetastasis of B16-F10 melanoma in micein vivo, as well as its molecular mechanisms of action using a high-throughput Cancer Pathway Finder PCR Array. ATA could not only induce tumor cells into apoptosis through the activation of both extrinsic and intrinsic pathways, arrest HepG2 cells in G2/M phase, but also suppress the invasion and metastasis abilities of HepG2 cells and the lung metastasis of B16-F10 melanoma in mice. PCR array assay revealed that ATA upregulated 9 genes including CDKN1A, MDM2, CFLAR (CASPER), TNFRSF10B (DR5), c-Jun, IL-8, THBS1, SERPINB5 (maspin), and TNF and downregulated 8 genes such as CCNE1, AKT, ANGPT1, TEK, TGFBR1, MMP9, U-PA, and S100A4. These results indicate that ATA could exert antitumor effects through activating JNK/MAPK and suppressing AKT signal transduction pathways and that ATA might be a potent anticancer agent.

scholarly journals Baicalein Potentiated M1 Macrophage Polarization in Cancer Through Targeting PI3Kγ/ NF-κB Signaling

2021 ◽  
Vol 12 ◽  
Author(s):  
Shan He ◽  
Shangshang Wang ◽  
Suqing Liu ◽  
Zheng Li ◽  
Xiao Liu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Macrophage Polarization ◽  
Inhibitory Effect ◽  
Binding Activity ◽  
Inflammatory Factors ◽  
Protein Kinase Activity ◽  
Antitumor Effects ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Underlying Mechanisms

Baicalein is one of the bioactive compounds extracted from Scutellaria baicalensis. Recent studies indicated the antitumor effects of baicalein, however, the underlying mechanisms are needed to be further determined. In this study, we found that baicalein could inhibit the tumor growth in mice models of breast cancer and melanoma and worked as an immunomodulator to promote the infiltration of tumor-associated macrophages (TAMs) and skew the TAMs towards the M1-like phenotype. Baicalein also induced M1-like phenotype polarization in THP-1-derived macrophages. Meanwhile, the expression of pro-inflammatory factors associated with M1 macrophages, including TNF-α, IL-1β, CXCL9 and CXCL10, were increased after baicalein treatment. Mechanistically, the RNA-seq data suggested that baicalein potentiated the M1 macrophage polarization via the NF-κB/TNF-α signaling pathway. ELISA and confocal microscopy assay confirmed that baicalein significantly induced the production of TNF-α and the activation of NF-κB, while TNF-α neutralization inhibited baicalein-induced macrophage polarization toward M1, and NF-κB P65 knock-down suppressed baicalein-induced TNF-α production in THP-1-derived macrophages. Phosphoinositide 3-kinase (PI3k) γ has been reported as a key molecule in macrophage polarization, and inhibition of PI3Kγ activates the NF-κB-related inflammatory signals. Our pharmacological network analysis predicted that PI3Kγ might be one of the major targets of baicalein. The results from the docking program and surface plasmon resonance (SPR) confirmed that baicalein displayed good binding activity to PI3Kγ. We further found that baicalein not only exhibited a direct inhibitory effect on the protein kinase activity of PI3Kγ, but also reduced the mRNA and protein expression of PI3Kγ, indicating that baicalein might be a novel PI3Kγ inhibitor. In summary, baicalein mediated the TAMs skewing to M1-TAMs, and then retarded tumor growth. These effects, at least in part, were linked to the PI3Kγ/NF-κB signaling.

Antitumor Effect of Zwitterions of Imidazolium Derived from L-methionine in BALB/c Mice with Lymphoma L5178Y

2020 ◽  
Vol 17 (1) ◽  
pp. 33-39
Author(s):  
Karen C. Vargas-Castro ◽  
Ana M. Puebla Pérez ◽  
Irma I. Rangel-Salas ◽  
Jorge I. Delgado-Saucedo ◽  
José B. Pelayo-Vázquez ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Antitumor Activity ◽  
Antitumor Agent ◽  
Inhibitory Effect ◽  
Stabilizing Agent ◽  
Biological Compatibility ◽  
In Vivo Tests ◽  
Antitumoral Agent ◽  
Group 1

Background: In the therapy of cancer, several treatments have been designed using nanomaterials, among which gold nanoparticles (AuNPs) have been featured as a promising antitumoral agent. Our research group has developed the synthesis of gold nanoparticles L-AuNPs and D-AuNPs stabilized with zwitterions of imidazolium (L-1 and D-1) derived from L-methionine and D-methionine. Because the stabilizer agent is chiral, we observed through circular dichroism that AuNPs also present chirality; such chirality as well as the fact that the stabilizing agent contains fragments of methionine and imidazolium that are commonly involved in biological processes, opens up the possibility that this system may have biological compatibility. Additionally, the presence of methionine in the stabilizing agent opens the application of this system as a possible antitumor agent because methionine is involved in methylation processes of molecules such as DNA. Objective: The aim of this research is the evaluation of the antitumor activity of gold nanoparticles stabilized with zwitterions of imidazolium (L-AuNPs) derived from L-methionine in the model of BALB/c mice with lymphoma L5178Y. Methods: Taking as a parameter cell density, the evaluation of the inhibitory effect of L-AuNPs was carried out with a series of in vivo tests in BALB/c type mice; three groups of five mice each were formed (Groups 1, 2 and 3); all mice were i.p. inoculated with the lymphoblast murine L5178Y. Group 1 consisted of mice without treatment. In the Groups 2 and 3 the mice were treated with L-AuNPs at 0.3 mg/Kg on days 1, 7 and 14 by orally and intraperitonally respectively. Results: These results show low antitumor activity of these gold nanoparticles (L-NPsAu) but interestingly, the imidazolium stabilizing agent of gold nanoparticle (L-1) displayed promising antitumor activity. On the other hand, the enantiomer of L-1, (D-1) as well as asymmetric imidazole derivate from L-methionine (L-2), do not exhibit the same activity as L-1. Conclusion: The imidazolium stabilizing agent (L-1) displayed promising antitumor activity. Modifications in the structure of L-1 showed that, the stereochemistry (like D-1) and the presence of methionine fragments (like L-2) are determinants in the antitumor activity of this compound.

scholarly journals RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen-Chen Huang ◽  
Fang-Rui Liu ◽  
Qiang Feng ◽  
Xin-Yan Pan ◽  
Shu-Ling Song ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Membrane ◽  
Fusion Protein ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Fusion Proteins ◽  
Inhibitory Effect ◽  
Endosomal Escape ◽  
Antitumor Effects ◽  
Sw480 Cells

Abstract Background We prepared an anti-p21Ras scFv which could specifically bind with mutant and wild-type p21Ras. However, it cannot penetrate the cell membrane, which prevents it from binding to p21Ras in the cytoplasm. Here, the RGD4C peptide was used to mediate the scFv penetration into tumor cells and produce antitumor effects. Methods RGD4C-EGFP and RGD4C-p21Ras-scFv recombinant expression plasmids were constructed to express fusion proteins in E. coli, then the fusion proteins were purified with HisPur Ni-NTA. RGD4C-EGFP was used as reporter to test the factors affecting RGD4C penetration into tumor cell. The immunoreactivity of RGD4C-p21Ras-scFv toward p21Ras was identified by ELISA and western blotting. The ability of RGD4C-p21Ras-scFv to penetrate SW480 cells and colocalization with Ras protein was detected by immunocytochemistry and immunofluorescence. The antitumor activity of the RGD4C-p21Ras-scFv was assessed with the MTT, TUNEL, colony formation and cell migration assays. Chloroquine (CQ) was used an endosomal escape enhancing agent to enhance endosomal escape of RGD4C-scFv. Results RGD4C-p21Ras-scFv fusion protein were successfully expressed and purified. We found that the RGD4C fusion protein could penetrate into tumor cells, but the tumor cell entry of was time and concentration dependent. Endocytosis inhibitors and a low temperature inhibited RGD4C fusion protein endocytosis into cells. The change of the cell membrane potential did not affect penetrability. RGD4C-p21Ras-scFv could penetrate SW480 cells, effectively inhibit the growth, proliferation and migration of SW480 cells and promote this cells apoptosis. In addition, chloroquine (CQ) could increase endosomal escape and improve antitumor activity of RGD4C-scFv in SW480 cells. Conclusion The RGD4C peptide can mediate anti-p21Ras scFv entry into SW480 cells and produce an inhibitory effect, which indicates that RGD4C-p21Ras-scFv may be a potential therapeutic antibody for the treatment of ras-driven cancers.

Activation of Selective Transcription Factors and Cytokines by Water-Soluble Extract from Lentinus lepideus

2003 ◽  
Vol 228 (6) ◽  
pp. 749-758 ◽  
Author(s):  
Mirim Jin ◽  
Hyung Jin Jung ◽  
Jeong June Choi ◽  
Hyang Jeon ◽  
Jin Hwan Oh ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Post Treatment ◽  
Water Soluble ◽  
Dependent Manner ◽  
Soluble Extract ◽  
Transient Transfection Assay ◽  
Gm Csf ◽  
Tnf Α ◽  
Water Soluble Extract

We isolated a water-soluble extract, PG101, from cultured mycelia of Lentinus lepideus. Treatment of human peripheral blood mononuclear cells (PBMCs) with PG101 increased levels of TNF-α, IL-1β, IL-10, and IL-12 by 100- to 1000-fold, whereas GM-CSF and IL-18 were activated by an order of magnitude. On the contrary, IFN-γ and IL-4 were not affected. The response to PG101 occurred in a dose- and time-dependent manner. From the human PBMCs treated with PG101, TNF-α was a first cytokine to be activated, detectable at 2 hr post-treatment followed by IL-1β at 6 hr post-treatment. IL-12 and IL-10 were the next to follow. GM-CSF and IL-18 both showed significant increases 24 hr after treatment. When PBMCs were sorted into various cell types, monocyte/macrophages, but not T and B cells, were the major target cell type responsive to PG101. Consistent with this result, the profile of cytokine expression upon PG101 treatment was comparable between PBMCs and a human promonocytic cell line (U937), whereas cell lines of T cell and myeloid origins did not respond to PG101. Data from a transient transfection assay involving specific reporter plasmids indicated that cellular transcription factor such as NF-κB, but not AP-1, was highly activated by PG101. Results from a gel retardation assay and the experiment involving a specific NF-κB inhibitor confirmed the involvement of NF-κB. Despite its significant biological effect on various cytokines, PG101 remained nontoxic in both rats and PBMCs even at a biological concentration approximately 20 times greater. PG101 demonstrates great potential as a therapeutic immune modulator.

scholarly journals Let-7a-5p regulates the inflammatory response in chronic rhinosinusitis with nasal polyps

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jianwei Zhang ◽  
Lei Han ◽  
Feng Chen
Keyword(s):  
Inflammatory Response ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Mapk Pathway ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Protein Levels ◽  
Tnf Α

Abstract Background Let-7a-5p is demonstrated to be a tumor inhibitor in nasopharyngeal carcinoma. However, the role of let-7a-5p in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been reported. This study is designed to determine the pattern of expression and role of let-7a-5p in CRSwNP. Methods The expression level of let-7a-5p, TNF-α, IL-1β, and IL-6 in CRSwNP tissues and cells were detected by RT-qPCR. Western blot assay was carried out to measure the protein expression of the Ras-MAPK pathway. Dual luciferase reporter assay and RNA pull-down assay were used to explore the relationship between let-7a-5p and IL-6. Results Let-7a-5p was significantly downregulated in CRSwNP tissues and cells. Moreover, the mRNA expression of TNF-α, IL-1β and IL-6 was increased in CRSwNP tissues, while let-7a-5p mimic inhibited the expression of TNF-α, IL-1β and IL-6. Besides that, let-7a-5p was negatively correlated with TNF-α, IL-1β and IL-6 in CRSwNP tissues. In our study, IL-6 was found to be a target gene of let-7a-5p. Additionally, let-7-5p mimic obviously reduced the protein levels of Ras, p-Raf1, p-MEK1 and p-ERK1/2, while IL-6 overexpression destroyed the inhibitory effect of let-7a-5p on the Ras-MAPK pathway in CRSwNP. Conclusion We demonstrated that let-7a-5p/IL-6 interaction regulated the inflammatory response through the Ras-MAPK pathway in CRSwNP.

scholarly journals The Phytochemical Analysis of Vinca L. Species Leaf Extracts Is Correlated with the Antioxidant, Antibacterial, and Antitumor Effects

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3040
Author(s):  
Alexandra Ciorîță ◽  
Cezara Zăgrean-Tuza ◽  
Augustin C. Moț ◽  
Rahela Carpa ◽  
Marcel Pârvu
Keyword(s):  
Bacterial Infections ◽  
Inhibitory Effect ◽  
Total Phenolic ◽  
Phytochemical Analysis ◽  
Leaf Extracts ◽  
Antitumor Effects ◽  
Cytotoxic Effects ◽  
E Coli ◽  
Lactate Dehydrogenase Release ◽  
Nitric Oxide Concentration

The phytochemical analysis of Vinca minor, V. herbacea, V. major, and V. major var. variegata leaf extracts showed species-dependent antioxidant, antibacterial, and cytotoxic effects correlated with the identified phytoconstituents. Vincamine was present in V. minor, V. major, and V. major var. variegata, while V. minor had the richest alkaloid content, followed by V. herbacea. V. major var. variegata was richest in flavonoids and the highest total phenolic content was found in V. herbacea which also had elevated levels of rutin. Consequently, V. herbacea had the highest antioxidant activity followed by V. major var. variegata. Whereas, the lowest one was of V. major. The V. minor extract showed the most efficient inhibitory effect against both Staphylococcus aureus and E. coli. On the other hand, V. herbacea had a good anti-bacterial potential only against S. aureus, which was most affected at morphological levels, as indicated by scanning electron microscopy. The Vinca extracts acted in a dose-depended manner against HaCaT keratinocytes and A375 melanoma cells and moreover, with effects on the ultrastructure, nitric oxide concentration, and lactate dehydrogenase release. Therefore, the Vinca species could be exploited further for the development of alternative treatments in bacterial infections or as anticancer adjuvants.

scholarly journals Apoptotic effect of novel pyrazolone-based derivative [Cu(PMPP-SAL)(EtOH)] on HeLa cells and its mechanism

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Delizhaer Reheman ◽  
Jing Zhao ◽  
Shan Guan ◽  
Guan-Cheng Xu ◽  
Yi-Jie Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Hela Cells ◽  
Copper Complexes ◽  
Antibacterial Properties ◽  
Inhibitory Effect ◽  
Parp Cleavage ◽  
Potential Candidate ◽  
Tnf Α

Abstract Pyrazolone complexes have strong anti-tumor and antibacterial properties, but the anti-tumor mechanism of pyrazolone-based copper complexes has not been fully understood. In this study, the possible mechanism and the inhibitory effect of a novel pyrazolone-based derivative compound [Cu(PMPP-SAL)(EtOH)] on human cervical cancer cells (HeLa cells) was investigated. [Cu(PMPP-SAL)(EtOH)] effectively inhibited proliferation of HeLa cells in vitro with an IC50 value of 2.082 after treatment for 72 h. Cell cycle analysis showed apoptosis was induced by blocking the cell cycle in the S phase. [Cu(PMPP-SAL)(EtOH)] promoted the loss of mitochondrial membrane potential, release of cytochrome c, PARP cleavage, and activation of caspase-3/9 in HeLa cells. Additionally, [Cu(PMPP-SAL)(EtOH)] inhibited the PI3K/AKT pathway and activated the P38/MAPK, and JNK/MAPK pathways. [Cu(PMPP-SAL)(EtOH)] also inhibited the phosphorylation of Iκ-Bα in the NF-κB pathway activated by TNF-α, thus restricting the proliferation of HeLa cells which were activated by TNF-α. In conclusion, [Cu(PMPP-SAL)(EtOH)] inhibited the growth of HeLa cells and induced apoptosis possibly via the caspase-dependent mitochondria-mediated pathway. These results suggest that [Cu(PMPP-SAL)(EtOH)] can be a potential candidate for the treatment of cervical cancer.

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