Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2018

Open Access 01-12-2018 | Research article

Dendritic cells pulsed with generated tumor cell lysate from Phyllanthus amarus Schum. & Thonn. induces anti-tumor immune response

Authors: Shimaa Ibrahim Abdelmenym Mohamed, Ibrahim Jantan, Mohd Azlan Nafiah, Mohamed Ali Seyed, Kok Meng Chan

Published in: BMC Complementary Medicine and Therapies | Issue 1/2018

Login to get access

Abstract

Background

Dendritic cells (DCs) are unique antigen presenting cells (APC) which play a pivotal role in immunotherapy and induction of an effective immune response against tumors. In the present study, 80% ethanol extract of Phyllanthus amarus was used to generate tumor lysate (TLY) derived from HCT 116 and MCF-7 cancer cell lines via induction of apoptosis. Monocyte-derived DCs were generated ex vivo from the adherent population of peripheral blood mononuclear cells (PBMCs). The generated TLY were used to impulse DCs to investigate its effect on their cellular immune functions including antigen presentation capacity, phagocytic activity, chemotaxis capacity, T-cell proliferation and cytokines release.

Methods

The effect of P. amarus-generated TLY on DCs maturation was evaluated by determination of MHC class I, II and CD 11c expression as well as the co-stimulatory molecules CD 83 and 86 by using flow cytometry. The phagocytic capacity of TLY-pulsed DCs was investigated through FITC-dextran uptake by using flow cytometry. The effect on the cytokines release including IL-12, IL-6 and IL-10 was elucidated by using ELISA. The migration capacity and T cell proliferation activity of pulsed DCs were measured. The relative gene expression levels of cytokines were determined by using qRT-PCR. The major constituents of P. amarus extract were qualitatively and quantitatively analyzed by using validated reversed-phase high performance liquid chromatography (HPLC) methods.

Results

P. amarus-generated TLY significantly up-regulated the expression levels of MHC class I, CD 11 c, CD 83 and 86 in pulsed DCs. The release of interleukin IL-12 and IL-6 was enhanced by TLY-DCs at a ratio of 1 DC: 3 tumor apoptotic bodies (APO), however, the release of IL-10 was suppressed. The migration ability as well as allogeneic T-cell proliferation activities of loaded DCs were significantly enhanced, but their phagocytic capacity was highly attenuated. The gene expression profiles for IL-12 and IL-6 of DCs showed increase in their mRNA gene expression in TLY pulsed DCs versus unloaded and LPS-treated only DCs.

Conclusion

The effect of P. amarus-generated TLY on the immune effector mechanisms of DCs verified its potential to induce an in vitro anti-tumor immune response against the recognized tumor antigen.
Literature
1.
2.
Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:203–8.CrossRef
3.
4.
Stockwin LH, McGonagle D, Martin IG, Blair GE. Dendritic cells: immunological sentinels with a central role in health and disease. Immunol Cell Biol. 2000;78(2):91–102.CrossRefPubMed
5.
Tugues S, Burkhard SH, Ohs I, Vrohlings M, Nussbaum K, Vom BJ. New insights into IL-12-mediated tumor suppression. Cell Death Differ. 2015;22(2):237–46.CrossRefPubMed
6.
Martínez-Lostao L, Anel A, Pardo J. How do cytotoxic lymphocytes kill cancer cells? Clin Cancer Res. 2015;21(22):5047–56.CrossRefPubMed
7.
8.
9.
Inaba K, Turley S, Yamaide F, Iyoda T, Mahnke K, Inaba M. Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. J Exp Med. 1998;188(11):2163–73.CrossRefPubMedPubMedCentral
10.
Trinchieri G. Interleukin-12: a proinflammatory cytokine with immuneregulatory functions that bridge innate resistence and antigen-specific adaptive immunity. Annu Rev Immunol. 1995;13:251–176.CrossRefPubMed
11.
Ma Y, Shurin GV, Peiyuan Z, Shurin MR. Dendritic cells in the cancer microenvironment. J Cancer. 2013;4(1):36–44.CrossRefPubMed
12.
13.
Grivennikov SI, Karin M. Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stage. Ann Rheum Dis. 2011;70:104–8.CrossRef
14.
Podrazil M, Horvath R, Becht E, Rozkova D, Bilkova P, Hromadkova H. Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer. Oncotarget. 2015;6(20):18192–205.CrossRefPubMedPubMedCentral
15.
Gray HJ, Benigno B, Berek J, Chang J, Mason J, Mileshkin L. Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial. J Immunother Cancer. 2016;4(1):34.CrossRefPubMedPubMedCentral
16.
Amin A, Dudek AZ, Logan TF, Lance RS, Holzbeierlein JM, Knox JJ. Survival with AGS-003, an autologous dendritic cell–based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): phase 2 study results. J Immunother Cancer. 2015;3(1):14.CrossRefPubMedPubMedCentral
17.
Dillman RO, Selvan SR, Schiltz PM, McClay EF, Barth NM, DePriest C. Phase II trial of dendritic cells loaded with antigens from self-renewing, proliferating autologous tumor cells as patient-specific antitumor vaccines in patients with metastatic melanoma: final report. Cancer Biother Radiopharm. 2009;24(3):311–9.CrossRefPubMed
18.
Mayanagi S, Kitago M, Sakurai T, Matsuda T, Fujita T, Higuchi H. Phase I pilot study of Wilms tumor gene 1 peptide-pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer. Cancer Sci. 2015;106(4):397–406.CrossRefPubMedPubMedCentral
19.
Polyzoidis S, Ashkan K. DCVax®-L - developed by northwest biotherapeutics. Hum Vaccines Immunother. 2014;10(11):3139–45.CrossRef
20.
Notka F, Meier GR, Wagner R. Inhibition of wild-type human immunodeficiency virus and reverse transcriptase inhibitor-resistant variants by Phyllanthus amarus. Antivir Res. 2003;58(2):175–86.CrossRefPubMed
21.
Yuandani, Ilangkovan M, Jantan I, Mohamad HF, Husain K, Abdul Razak AF. Inhibitory effects of standardized extracts of Phyllanthus amarus and Phyllanthus urinaria and their marker compounds on phagocytic activity of human neutrophils. Evidence-based Complement Altern Med. 2013;2013:603634.CrossRef
22.
Bhat SS, Hegde KS, Chandrashekhar S, Rao SN, Manikkoth S. Preclinical screening of Phyllanthus amarus ethanolic extract for its analgesic and antimicrobial activity. Pharm Res. 2015;7(4):378–84.
23.
Lawson-Evi P, Eklu-Gadeg K, Agbonon A, Aklikokou K, Creppy E, Gbeassor M. Antidiabetic activity of Phyllanthus amarus Schum. And Thonn. (Euphorbiaceae) on alloxan induced diabetes in male wistar rats. J Appl Sci. 2011;11(16):2968–73.CrossRef
24.
Abhyankar G, Suprasanna P, Pandey BN, Mishra KP, Rao KV, Reddy VD. Hairy root extract of Phyllanthus amarus induces apoptotic cell death in human breast cancer cells. Innov Food Sci Emerg Technol. 2010;11(3):526–32.CrossRef
25.
Lee SH, Jaganath IB, Wang SM, Sekaran SD. Antimetastatic effects of Phyllanthus on human lung (A549) and breast (MCF-7) cancer cell lines. PLoS One. 2011;6(6):1–14.
26.
Jantan I, Ilangkovan M, Mohamad HF. Correlation between the major components of Phyllanthus amarus and Phyllanthus urinaria and their inhibitory effects on phagocytic activity of human neutrophils. Evidence-based Complement Altern Med. 2014;14:1–12.CrossRef
27.
Henry F, Boisteau O, Bretaudeau L, Lieubeau B, Meflah K, Grégoire M. Antigen-presenting cells that phagocytose apoptotic tumor-derived cells are potent tumor vaccines. Cancer Res. 1999;59(14):3329–32.PubMed
28.
29.
Zajac AJ, Blattman JN, Murali-Krishna K, Sourdive DJ, Suresh M, Altman JD. Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med. 1998;188(12):2205–13.CrossRefPubMedPubMedCentral
30.
31.
Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RAB, Henson PM. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature. 2000;405(6782):85–90.CrossRefPubMed
32.
Idoyaga J, Moreno J, Bonifaz L. Tumor cells prevent mouse dendritic cell maturation induced by TLR ligands. Cancer Immunol Immunother. 2007;56(8):1237–50.CrossRefPubMed
33.
Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002;418(6894):191–5.CrossRefPubMed
34.
Strome SE, Voss S, Wilcox R, Wakefield TL, Tamada K, Flies D. Strategies for antigen loading of dendritic cells to enhance the antitumor immune response. Cancer Res. 2002;62(6):1884–9.PubMed
35.
Parvathaneni M, Battu GR, Gray AI, Gummalla P. Investigation of anticancer potential of hypophyllanthin and phyllanthin against breast cancer by in vitro and in vivo methods. Asian Pacific J Trop Dis. 2014;4(S1):930–5.
36.
Pang JHS, Huang ST, Wang CY, Yang RC, Wu HT, Yang SH. Ellagic acid, the active compound of Phyllanthus urinaria, exerts in vivo anti-angiogenic effect and inhibits MMP-2 activity. Evidence-based Complement Altern Med. 2011;2011:1–11.
37.
Bin-Chuan JI, Hsu WH, Yang JS, Hsia TC, Lu CC, Chiang JH. Gallic acid induces apoptosis via caspase-3 and mitochondrion-dependent pathways in vitro and suppresses lung xenograft tumor growth in vivo. J Agric Food Chem. 2009;57(16):7596–604.CrossRef
38.
Hatfield P, Merrick AE, West E, OʼDonnell D, Selby P, Vile R. Optimization of dendritic cell loading with tumor cell lysates for cancer immunotherapy. J Immunother. 2008;31(7):620–32.CrossRefPubMedPubMedCentral
39.
Fields RC, Shimizu K, Mulé JJ. Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo. Proc Natl Acad Sci U S A. 1998;95(16):9482–7.CrossRefPubMedPubMedCentral
40.
Sharma A, Koldovsky U, Xu S, Mick R, Roses R, Fitzpatrick E. HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ. Cancer. 2012;118(17):4354–62.CrossRefPubMedPubMedCentral
41.
Czerniecki BJ, Koski GK, Koldovsky U, Xu S, Cohen PA, Mick R. Targeting HER-2/neu in early breast cancer development using dendritic cells with staged Interleukin-12 burst secretion. Cancer Res. 2007;67(4):1842–52.CrossRefPubMed
42.
Bonham CA, Lu L, Banas RA, Fontes P, Rao AS, Starzl TE. TGF-β1 pretreatment impairs the allostimulatory function of human bone marrow-derived antigen-presenting cells for both naive and primed T cells. Transpl Immunol. 1996;4(3):186–91.CrossRefPubMedPubMedCentral
43.
Sallusto F, Cella M, Danieli C, Lanzavecchia A. Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class 1I compartment: downregulation by cytokines and bacterial products. J Exp Med. 1995;182:389–400.CrossRefPubMed
44.
Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O’Garra A, Murphy KM. Development of TH1 CD4+ T cells through IL-12 produced by listeria-induced macrophages. Science. 1993;260(5107):547–9.CrossRefPubMed
45.
Vanden Bush TJ, Buchta CM, Claudio J, Bishop GA. Cutting edge: importance of IL-6 and cooperation between innate and adaptive immune receptors in cellular vaccination with B lymphocytes. J Immunol. 2009;183(8):4833–7.CrossRefPubMed
46.
Gagnon J, Ramanathan S, Leblanc C, Cloutier A, McDonald PP, Ilangumaran S. IL-6, in synergy with IL-7 or IL-15, stimulates TCR-independent proliferation and functional differentiation of CD8+ T lymphocytes. J Immunol. 2008;180(12):7958–68.CrossRefPubMed
47.
Teague TK, Marrack P, Kappler JW, Vella AT. IL-6 rescues resting mouse T cells from apoptosis. J Immunol. 1997;158(12):5791–6.PubMed
48.
Mohamed SIA, Jantan I, Haque MA. Naturally occurring immunomodulators with antitumor activity: an insight on their mechanisms of action. Int Immunopharmacol. 2017;50:291–304.CrossRefPubMed
49.
Zhang X, Huang H, Yuan J, Sun D, Hou W-S, Gordon J. CD4-8- dendritic cells prime CD4+ T regulatory 1 cells to suppress antitumor immunity. J Immunol. 2005;175(5):2931–7.CrossRefPubMed
50.
Vopenkova K, Mollova K, Buresova I, Michalek J. Complex evaluation of human monocyte-derived dendritic cells for cancer immunotherapy. J Cell Mol Med. 2012;16(11):2827–37.CrossRefPubMedPubMedCentral
Metadata
Title
Dendritic cells pulsed with generated tumor cell lysate from Phyllanthus amarus Schum. & Thonn. induces anti-tumor immune response
Authors
Shimaa Ibrahim Abdelmenym Mohamed
Ibrahim Jantan
Mohd Azlan Nafiah
Mohamed Ali Seyed
Kok Meng Chan
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2018
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-018-2296-4

Other articles of this Issue 1/2018

BMC Complementary Medicine and Therapies 1/2018 Go to the issue

Study protocol

Efficacy of self-management exercise program with spa therapy for behavioral management of knee osteoarthritis: research protocol for a quasi-randomized controlled trial (GEET one)

Research article

Does Jacobson’s relaxation technique reduce consumption of psychotropic and analgesic drugs in cancer patients? A multicenter pre–post intervention study

Research article

Dual function of active constituents from bark of Ficus racemosa L in wound healing

Research article

Anti-Brucella activity of Caryopteris mongolica Bunge root extract against Brucella melitensis infection in mice

Research article

Use of biologically-based complementary medicine in breast and gynecological cancer patients during systemic therapy

Research article

In vitro antileishmanial and cytotoxicity activities of essential oils from Haplophyllum tuberculatum A. Juss leaves, stems and aerial parts