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
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
Clinical Oral Investigations
Published in: Clinical Oral Investigations 1/2017

Open Access 01-01-2017 | Original Article

Triptolide represses oral cancer cell proliferation, invasion, migration, and angiogenesis in co-inoculation with U937 cells

Authors: Cheng-Yu Yang, Chih-Kung Lin, Gu-Jiun Lin, Cheng-Chih Hsieh, Shing-Hwa Huang, Kuo-Hsing Ma, Yi-Shing Shieh, Huey-Kang Sytwu, Yuan-Wu Chen

Published in: Clinical Oral Investigations | Issue 1/2017

Login to get access

Abstract

Objectives

Advanced oral cancer is a major public health concern because of a lack of effective prevention and treatment. Triptolide (TPL), a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, has been demonstrated to possess strong anticancer properties. In this study, we investigated whether TPL exerts anticancer effects on the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC).

Materials and methods

Human macrophage-like U937 cells were co-inoculated with oral cancer SAS cells in a noncontact transwell coculture system. Cytokine expression was detected using ELISA, and cell proliferation was detected using methylene blue. RNA levels were detected using qPCR. Protein levels were detected using Western blot analysis. In vivo experiments involved using xenografted NOD/SCID mice.

Results

Our results demonstrated that TPL inhibited the growth of SAS cells co-inoculated with U937 cells in vitro and in vivo. TPL inhibited the invasion, migration ability, and angiogenesis of SAS cells co-inoculated with U937 cells. Expression of cytokines IL-6, IL-8, and TNF-α was induced by co-inoculation, but TPL repressed their expression.

Conclusion

TPL suppressed the expression of cytokines IL-6, IL-8, and TNF-α, as well as tumor growth, invasion, migration, and angiogenesis in the co-inoculation of human tongue cancer cells with macrophage-like U937 cells.

Clinical relevance

TPL is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating tumor-associated macrophages in a tumor microenvironment of HNSCC.
Literature
1.
Pentenero M, Gandolfo S, Carrozzo M (2005) Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral squamous cell carcinoma: a review of the literature. Head Neck 27(12):1080–1091CrossRefPubMed
2.
Chen YJ et al. (2004) Genome-wide profiling of oral squamous cell carcinoma. J Pathol 204(3):326–332CrossRefPubMed
3.
Daley T, Darling M (2003) Nonsquamous cell malignant tumours of the oral cavity: an overview. J can Dent Assoc 69(9):577–582PubMed
4.
Lyons AJ, Jones J (2007) Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma. Int J Oral Maxillofac Surg 36(8):671–679CrossRefPubMed
5.
Jemal A et al. (2009) Cancer statistics 2009. Ca Cancer J Clin, 59(4):225–249CrossRef
6.
Condeelis J, Pollard JW (2006) Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124(2):263–266CrossRefPubMed
7.
Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res 66(2):605–612CrossRefPubMed
8.
El-Rouby DH (2010) Association of macrophages with angiogenesis in oral verrucous and squamous cell carcinomas. J Oral Pathol Med 39(7):559–564CrossRefPubMed
9.
Chen YW et al. (2009) Triptolide exerts anti-tumor effect on oral cancer and KB cells in vitro and in vivo. Oral Oncol 45(7):562–568CrossRefPubMed
10.
Herzog A et al. (2013) PI3K/mTOR inhibitor PF-04691502 antitumor activity is enhanced with induction of wild-type TP53 in human xenograft and murine knockout models of head and neck cancer. Clin Cancer Res 19(14):3808–3819CrossRefPubMedPubMedCentral
11.
Ou CC et al. (2012) Triptolide transcriptionally represses HER2 in ovarian cancer cells by targeting NF-kappaB. Evid Based Complement Alternat Med 2012:350239PubMedPubMedCentral
12.
Chen YW et al. (2014) Enhanced anti-tumor activity of triptolide in combination with irradiation for the treatment of oral cancer. Planta Med 80(4):255–261CrossRefPubMed
13.
Lo JF et al. (2011) The epithelial-mesenchymal transition mediator S100A4 maintains cancer-initiating cells in head and neck cancers. Cancer Res 71(5):1912–1923CrossRefPubMed
14.
Kumar R et al. (2012) Correction: co-culture of retinal and endothelial cells results in the modulation of genes critical to retinal neovascularization. Vasc Cell 4:6CrossRefPubMedPubMedCentral
15.
Craig M, Ying C, Loberg RD (2008) Co-inoculation of prostate cancer cells with U937 enhances tumor growth and angiogenesis in vivo. J Cell Biochem 103(1):1–8CrossRefPubMed
16.
Gialeli C, Theocharis AD, Karamanos NK (2011) Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting. Febs J 278(1):16–27CrossRefPubMed
17.
Yang S et al. (2011) Inhibitive effect of triptolide on invasiveness of human fibrosarcoma cells by downregulating matrix metalloproteinase-9 expression. Asian Pac J Trop Med 4(6):482–485CrossRefPubMed
18.
Zhao H et al. (2012) Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin. Exp Mol Med 44(11):633–641CrossRefPubMedPubMedCentral
19.
Ma JX et al. (2013) Triptolide induces apoptosis and inhibits the growth and angiogenesis of human pancreatic cancer cells by downregulating COX-2 and VEGF. Oncol Res 20(8):359–368CrossRefPubMed
20.
Kishimoto T (2005) Interleukin-6: from basic science to medicine—40 years in immunology. Annu Rev Immunol 23:1–21CrossRefPubMed
21.
Chen Z et al. (1999) Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res 5(6):1369–1379PubMed
22.
Duffy SA et al. (2008) Interleukin-6 predicts recurrence and survival among head and neck cancer patients. Cancer 113(4):750–757CrossRefPubMed
23.
Kotyza J (2012) Interleukin-8 (CXCL8) in tumor associated non-vascular extracellular fluids: its diagnostic and prognostic values. A review. Int J Biol Markers 27(3):169–178CrossRefPubMed
24.
Desai S, Laskar S, Pandey BN (2013) Autocrine IL-8 and VEGF mediate epithelial-mesenchymal transition and invasiveness via p38/JNK-ATF-2 signalling in A549 lung cancer cells. Cell Signal 25(9):1780–1791CrossRefPubMed
25.
Waters JP, Pober JS, Bradley JR (2013) Tumour necrosis factor in infectious disease. J Pathol 230(2):132–147CrossRefPubMed
26.
Aggarwal BB, Gupta SC, Kim JH (2012) Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood 119(3):651–665CrossRefPubMedPubMedCentral
27.
Li M, You Q, Wang X (2011) Association between polymorphism of the tumor necrosis factor alpha-308 gene promoter and colon cancer in the Chinese population. Genet Test Mol Biomarkers 15(11):743–747CrossRefPubMed
Metadata
Title
Triptolide represses oral cancer cell proliferation, invasion, migration, and angiogenesis in co-inoculation with U937 cells
Authors
Cheng-Yu Yang
Chih-Kung Lin
Gu-Jiun Lin
Cheng-Chih Hsieh
Shing-Hwa Huang
Kuo-Hsing Ma
Yi-Shing Shieh
Huey-Kang Sytwu
Yuan-Wu Chen
Publication date
01-01-2017
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 1/2017
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-016-1808-1

Other articles of this Issue 1/2017

Clinical Oral Investigations 1/2017 Go to the issue

Review

Serum antibody levels against Porphyromonas gingivalis in patients with and without rheumatoid arthritis – a systematic review and meta-analysis

Original Article

Novel FGF10 mutation in autosomal dominant aplasia of lacrimal and salivary glands

Original Article

Effect of hyperbaric oxygen therapy on tooth extraction sites in rats subjected to bisphosphonate therapy—histomorphometric and immunohistochemical analysis

Original Article

In situ effect of a CPP-ACP chewing gum on enamel erosion associated or not with abrasion

Original Article

A novel flapless approach versus minimally invasive surgery in periodontal regeneration with enamel matrix derivative proteins: a 24-month randomized controlled clinical trial

Original Article

In vitro antibacterial and remineralizing effect of adhesive containing triazine and niobium pentoxide phosphate inverted glass