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

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2021

Open Access 01-12-2021 | Active Ingredients | Primary research

Huanglianjiedu Decoction as an effective treatment for oral squamous cell carcinoma based on network pharmacology and experimental validation

Authors: Lejun Zhang, Zhaoting Ling, Zhengqiang Hu, Guanmin Meng, Xinqiang Zhu, Huifang Tang

Published in: Cancer Cell International | Issue 1/2021

Login to get access

Abstract

Background

Oral squamous cell carcinoma (OSCC) is one of malignant tumors in oral and maxillofacial region with high fatality. Huanglianjiedu Decoction (HLJDD) is a well-known traditional Chinese medicinal prescription, which consists of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Phellodendron amurense Rupr and Gardenia jasminoides J.Ellis. Some clinical studies showed HLJDD had good effectiveness on OSCC, but the mechanism is unclear.

Methods

In this study, potential components of HLJDD and putative targets were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Combining with potential targets of OSCC searched from Therapeutic Target Database (TTD) and Online Mendelian Inheritance in Man (OMIM), we drew protein–protein interaction (PPI) network by Cytoscape v3.2.0 software. After topological analysis we got core targets and further did Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then we did the in vitro experiments to verify the major biological processes (cell cycle, apoptosis and proliferation) and signaling pathways (mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), protein kinase B (AKT)) on OSCC cell lines, SCC-25 and CAL-27.

Results

The potential component targets number of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Phellodendron amurense Rupr and Gardenia jasminoides J.Ellis were 39, 93, 81and 88, respectively. Then we got 52 core targets which enriched in cell cycle, apoptosis, proliferation, MAPK activation etc. and obtained TOP30 pathways. On SCC-25 and CAL-27, HLJDD suppressed cell proliferation, induced late apoptosis and inhibited cell invasion and migration which were consistent with the results from network pharmacology analysis. Additionally, in cell cycle, we confirmed HLJDD inhibited G1 phase and arrested in S phase to reduce cell proliferation on SCC-25. In signaling pathways, HLJDD inhibited the phosphorylation of extracellular regulatory protein kinase 1/2 (ERK1/2) and NF-κB p65 (S468) on SCC-25 and CAL-27.

Conclusions

HLJDD played a potential therapeutic role on OSCC via inhibiting p-ERK1/2 and p-NF-κB p65 (S468).

Graphical abstract

Appendix
Available only for authorised users
Literature
1.
Thomson PJ. Perspectives on oral squamous cell carcinoma prevention—proliferation, position, progression and prediction. J Oral Pathol Med. 2018;47:803–7.CrossRef
2.
Da SSD, Ferlito A, Takes RP, Brakenhoff RH, Valentin MD, Woolgar JA, et al. Advances and applications of oral cancer basic research. Oral Oncol. 2011;47:783–91.CrossRef
3.
Wheeler SE, Shi H, Lin F, Dasari S, Bednash J, Thorne S, et al. Tumor associated fibroblasts enhance head and neck squamous cell carcinoma proliferation, invasion, and metastasis in preclinical models. Head Neck. 2015;36:385–92.CrossRef
4.
Yadav P. Recent advances in head and neck cancer reconstruction. Indian J Plast Surg. 2014;47:185–90.CrossRef
5.
Caponigro F, Milano A, Basile M, Ionna F, Iaffaioli RV. Recent advances in head and neck cancer therapy: the role of new cytotoxic and molecular-targeted agents. Curr Opin Oncol. 2006;18:247–52.CrossRef
6.
Williams MD. Integration of biomarkers including molecular targeted therapies in head and neck cancer. Head Neck Pathol. 2010;4:62–9.CrossRef
7.
8.
Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008;4:682–90.CrossRef
9.
Chen Y, Dong J, Liu J, Xu W, Wei Z, Li Y, et al. Network pharmacology-based investigation of protective mechanism of Aster tataricus on lipopolysaccharide-induced acute lung injury. Int J Mol Sci. 2019;20:1–17.
10.
Li T, Baochen Z, Yue Z, Cheng W, Yali W, Zongxi S, et al. Network Pharmacology-Based identification of pharmacological mechanism of SQFZ injection in combination with Docetaxel on lung cancer. Sci Rep. 2019;9:1–12.
11.
Kulshrestha A, Suman S, Ranjan R. Network analysis reveals potential markers for pediatric adrenocortical carcinoma. Onco Targets Ther. 2016;9:4569–81.CrossRef
12.
Ma C, Xu T, Sun X, Zhang S, Liu S, Fan S, et al. Network pharmacology and bioinformatics approach reveals the therapeutic mechanism of action of baicalein in hepatocellular carcinoma. Evid Based Comp Altern Med. 2019;2019:1–15.
13.
Li J, Lu C, Jiang M, Niu X, Guo H, Li L, et al. Traditional chinese medicine-based network pharmacology could lead to new multicompound drug discovery. Evid Based Comp Altern Med. 2012;2012:1–11.
14.
15.
Liu L, Jiang P, Dong SS, Liu RH, Zhang C, Zhang WD. Advances in studies on chemical constituents in Huanglian Jiedu Tang and their pharmacology. Chinese Tradit Herb Drugs. 2008;39:935–8 (in Chinese).
16.
Zheng Y, Cheng XR, Zhou WX, Zhang YX. Gene expression patterns of hippocampus and cerebral cortex of senescence-accelerated mouse treated with Huang-Lian-Jie-Du decoction. Neurosci Lett. 2008;439:119–24.CrossRef
17.
Ye Y, Huang C, Jiang L, Shen X, Zhu S, Rao Y, et al. Huanglian-Jie-Du-Tang extract protects against chronic brain injury after focal cerebral ischemia via hypoxia-inducible-factor-1α-regulated vascular endothelial growth factor signaling in mice. Biol Pharm Bull. 2012;35:355–61.CrossRef
18.
Ohta Y, Kobayashi T, Nishida K, Sasaki E, Ishiguro I. Preventive effect of Oren-gedoku-to (Huanglian-Jie-Du-Tang) extract on the development of stress-induced acute gastric mucosal lesions in rats. J Ethnopharmacol. 1999;67:377–84.CrossRef
19.
Xu Y, Guo S, Chen G, Zhang M, Zhang X, Dou D. Evaluation of anti-sepsis activity by compounds with high affinity to lipid a from HuanglianJiedu decoction. Immunopharmacol Immunotoxicol. 2017;39:364–70.CrossRef
20.
Chen Y, Xian Y, Lai Z, Loo S, Chan WY, Lin ZX. Anti-inflammatory and anti-allergic effects and underlying mechanisms of Huang-Lian-Jie-Du extract: implication for atopic dermatitis treatment. J Ethnopharmacol Elsevier. 2016;185:41–52.CrossRef
21.
Sun J, Wen QH, Song Y, Li X, Jin J. Study on antitumor activities of Huanglian Jiedu decoction. China J Chinese Mater Medica. 2006;31:1461–3 (in Chinese).
22.
Wu XD, Wang YL. 30 cases of tongue cancer with Admixture of Huanglian Jiedu Decoction treatment. Shanxi Tradit Chinese Med. 2002;23:1078 (in Chinese).
23.
Wang N, Feng Y, Tan HY, Cheung F, Hong M, Lao L, et al. Inhibition of eukaryotic elongation factor-2 confers to tumor suppression by a herbal formulation Huanglian-Jiedu decoction in human hepatocellular carcinoma. J Ethnopharmacol. 2015;164:309–18.CrossRef
24.
Ru J, Li P, Wang J, Zhou W, Li B, Huang C, et al. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014;6:1–6.CrossRef
25.
Li YH, Yu CY, Li XX, Zhang P, Tang J, Yang Q, et al. Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics. Nucleic Acids Res. 2018;46:D1121–7.CrossRef
26.
Bateman A, Martin MJ, O’Donovan C, Magrane M, Apweiler R, Alpi E, et al. UniProt: a hub for protein information. Nucleic Acids Res. 2015;43:D204–12.CrossRef
27.
Amberger JS, Bocchini CA, Schiettecatte F, Scott AF, Hamosh A. OMIM.org: online Mendelian Inheritance in Man (OMIM®), an Online catalog of human genes and genetic disorders. Nucleic Acids Res. 2015;43:789–98.CrossRef
28.
Li L, Lei Q, Zhang S, Kong L, Qin B. Screening and identification of key biomarkers in hepatocellular carcinoma: evidence from bioinformatic analysis. Oncol Rep. 2017;38:2607–18.CrossRef
29.
Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013;41:808–15.CrossRef
30.
Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44–57.CrossRef
31.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models. Genome Res. 1971;13:2498–504.CrossRef
32.
33.
34.
Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009;25:1091–3.CrossRef
35.
36.
37.
Wang WT, Chen YH, Hsu JL, Leu WJ, Yu CC, Chan SH, et al. Terfenadine induces anti-proliferative and apoptotic activities in human hormone-refractory prostate cancer through histamine receptor-independent Mcl-1 cleavage and Bak up-regulation. Naunyn Schmiedebergs Arch Pharmacol. 2014;387:33–45.CrossRef
38.
Zuo R, Wang HJ, Si N, Zhao HY, Yang J, Bian BL. LC-FT-ICR-MS analysis of the prototypes and metabolites in rat plasma after administration of Huang-Lian-Jie-Du Decoction. Acta Pharm Sin. 2014;49:237–43 (in Chinese).
39.
Li Z, Chen L, Xie R, Zhou X. Establishment of quality evaluation system of Huang 1ian Jiedu decoction based on fingerprint technology and comprehensive scoring method. Guid J TCM. 2020;26:28–35 (in Chinese).
40.
41.
42.
Wang S, Wang H, Lu Y. Tianfoshen oral liquid: a CFDA approved clinical traditional Chinese medicine, normalizes major cellular pathways disordered during colorectal carcinogenesis. Oncotarget. 2017;8:14549–69.CrossRef
43.
Wu K, Wei P, Liu M, Liang X, Su M. To reveal pharmacological targets and molecular mechanisms of curcumol against interstitial cystitis. J Adv Res. 2019;20:43–50.CrossRef
44.
Wu H, Li L, Ai Z, Yin J, Chen L. Pristimerin induces apoptosis of oral squamous cell carcinoma cells via G 1 phase arrest and MAPK/ErK1/2 and AKt signaling inhibition. Oncol Lett. 2019;17:3017–25.PubMedPubMedCentral
45.
Tsov S, Skvortsova I, Stasyk T, Schiefermeier N, Neher A, Gunkel AR, et al. Antitumor activity of CTFB, a novel anticancer agent, is associated with the down-regulation of nuclear factor-κB expression and proteasome activation in head and neck squamous carcinoma cell lines. Mol Cancer Ther. 2007;6:1898–908.CrossRef
Metadata
Title
Huanglianjiedu Decoction as an effective treatment for oral squamous cell carcinoma based on network pharmacology and experimental validation
Authors
Lejun Zhang
Zhaoting Ling
Zhengqiang Hu
Guanmin Meng
Xinqiang Zhu
Huifang Tang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2021
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-021-02201-6

Other articles of this Issue 1/2021

Cancer Cell International 1/2021 Go to the issue

Review

Mismatch repair-deficient hormone receptor-positive breast cancers: Biology and pathological characterization

Primary research

Dynamic serum biomarkers to predict the efficacy of PD-1 in patients with nasopharyngeal carcinoma

Primary research

Identification of differential proteomics in Epstein-Barr virus-associated gastric cancer and related functional analysis

Primary research

Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma

Correction

Correction to: EZH2 promotes the expression of LPA1 by mediating microRNA-139 promoter methylation to accelerate the development of ovarian cancer

Review

Nanobodies: a tool to open new horizons in diagnosis and treatment of prostate cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits