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 STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Esophageal Cancer | Primary research

Sulforaphene induces apoptosis and inhibits the invasion of esophageal cancer cells through MSK2/CREB/Bcl-2 and cadherin pathway in vivo and in vitro

Authors: Chengjuan Zhang, Junxia Zhang, Qiong Wu, Benling Xu, Guoguo Jin, Yan Qiao, Simin Zhao, Yang Yang, Jinwen Shang, Xiaofang Li, Kangdong Liu

Published in: Cancer Cell International | Issue 1/2019

Login to get access

Abstract

Background

As a novel type of isothiocyanate derived from radish seeds from cruciferous vegetables, sulforaphene (SFE, 4-methylsufinyl-3-butenyl isothiocyanate) has various important biological effects, such as anti-oxidative and anti-bacterial effects. Recently, sulforaphene has attracted increasing attention for its anti-tumor effects and its ability to suppress the development of multiple tumors through different regulatory mechanisms. However, it has not yet been widely investigated for the treatment of esophageal cancer.

Methods

We observed an increased apoptosis in esophageal cancer cells on sulforaphene treatment through flow cytometry (FCM) analysis and transmission electron microscopy (TEM). Through mass spectrometry (MS) analysis, we further detected global changes in the proteomes and phosphoproteomes of esophageal cancer cells on sulforaphene treatment. The molecular mechanism of sulforaphene was verified by western blot,the effect and mechanism of SFE on esophageal cancer was further verified by patient-derived xenograft mouse model.

Results

We identified multiple cellular processes that were changed after sulforaphene treatment by proteomics. We found that sulforaphene could repress the phosphorylation of CREB through MSK2, leading to suppression of Bcl-2 and further promoted cell apoptosis. Additionally, we confirmed that sulforaphene induces tumor cell apoptosis in mice. Interestingly, we also observed the obvious inhibition of cell migration and invasion caused by sulforaphene treatment by inhibiting the expression of cadherin, indicating the complex effects of sulforaphene on the development of esophageal cancer.

Conclusions

Our data demonstrated that sulforaphene induced cell apoptosis and inhibits the invasion of esophageal cancer through a mechanism involving the inhibition of the MSK2–CREB–Bcl2 and cadherin pathway. Sulforaphene could therefore serve as a promising anti-tumor drug for the treatment of esophageal cancer.
Literature
1.
Mizuta H, et al. Predictive factors for esophageal stenosis after endoscopic submucosal dissection for superficial esophageal cancer. Dis Esophagus. 2009;22(7):626–31.PubMedCrossRef
2.
Di Pardo BJ, et al. The global burden of esophageal cancer: a disability-adjusted life-year approach. World J Surg. 2016;40(2):395–401.PubMedCrossRef
3.
Lu HB. MicroRNA-556-3p promotes the progression of esophageal cancer via targeting DAB2IP. Eur Rev Med Pharmacol Sci. 2018;22(20):6816–23.PubMed
4.
Zhang SW, et al. Mortality and survival analysis of esophageal cancer in China. Zhonghua Zhong Liu Za Zhi. 2016;38(9):709–15.PubMed
5.
He Y, et al. Incidence and mortality rate of esophageal cancer has decreased during past 40 years in Hebei Province, China. Chin J Cancer Res. 2015;27(6):562–71.PubMedPubMedCentral
6.
Wang M, et al. Distribution of esophageal squamous cell cancer and precursor lesions in high-risk areas, Linzhou in Henan province and Feicheng in Shandong province of China, 2005–2009. Zhonghua Yu Fang Yi Xue Za Zhi. 2015;49(8):677–82.PubMed
7.
Sun X, et al. The long-term spatial-temporal trends and burden of esophageal cancer in one high-risk area: a population-registered study in Feicheng, China. PLoS ONE. 2017;12(3):e0173211.PubMedPubMedCentralCrossRef
8.
Duan XF, et al. The prevalence of lymph node metastasis for pathological T1 esophageal cancer: a retrospective study of 143 cases. Surg Oncol. 2018;27(1):1–6.PubMedCrossRef
9.
Yang Z, et al. Upregulation of PDK1 associates with poor prognosis in esophageal squamous cell carcinoma with facilitating tumorigenicity in vitro. Med Oncol. 2014;31(12):337.PubMedCrossRef
10.
Zhang L, et al. Targeted therapy in esophageal cancer. Expert Rev Gastroenterol Hepatol. 2016;10(5):595–604.PubMedCrossRef
11.
12.
Wang F, Fan QX. Current status and future prospect of internal medicine treatment for advanced esophageal cancer. Zhonghua Zhong Liu Za Zhi. 2016;38(9):655–9.PubMed
13.
Chatterjee S, et al. Sulforaphene enhances the efficacy of photodynamic therapy in anaplastic thyroid cancer through Ras/RAF/MEK/ERK pathway suppression. J Photochem Photobiol B. 2018;179:46–53.PubMedCrossRef
14.
Chen J, et al. Sulforaphene inhibition of adipogenesis via hedgehog signaling in 3T3-L1 adipocytes. J Agric Food Chem. 2018;66(45):11926–34.PubMedCrossRef
15.
Wang H, et al. Traditional herbal medicine-derived sulforaphene promotes mitophagic cell death in lymphoma cells through CRM1-mediated p62/SQSTM1 accumulation and AMPK activation. Chem Biol Interact. 2018;281:11–23.PubMedCrossRef
16.
He C, et al. Sulforaphane attenuates homocysteine-induced endoplasmic reticulum stress through Nrf-2-driven enzymes in immortalized human hepatocytes. J Agric Food Chem. 2014;62(30):7477–85.PubMedCrossRef
17.
Ko MO, Kim MB, Lim SB. Relationship between chemical structure and antimicrobial activities of isothiocyanates from cruciferous vegetables against oral pathogens. J Microbiol Biotechnol. 2016;26(12):2036–42.PubMedCrossRef
18.
Shishu, Singla AK, Kaur IP. Inhibition of mutagenicity of food-derived heterocyclic amines by sulphoraphene—an isothiocyanate isolated from radish. Planta Med. 2003;69(2):184–6.PubMedCrossRef
19.
Bao C, et al. Sulforaphene interferes with human breast cancer cell migration and invasion through inhibition of hedgehog signaling. J Agric Food Chem. 2016;64(27):5515–24.PubMedCrossRef
20.
Biswas R, Ahn JC, Kim JS. Sulforaphene synergistically sensitizes cisplatin via enhanced mitochondrial dysfunction and PI3K/PTEN modulation in ovarian cancer cells. Anticancer Res. 2015;35(7):3901–8.PubMed
21.
Ren K, et al. Sulforaphene enhances radiosensitivity of hepatocellular carcinoma through suppression of the NF-kappaB pathway. J Biochem Mol Toxicol. 2017;31(8):e21917.CrossRef
22.
Chatterjee S, Rhee YH, Ahn JC. Sulforaphene-carboplatin combination synergistically enhances apoptosis by disruption of mitochondrial membrane potential and cell cycle arrest in human non-small cell lung carcinoma. J Med Food. 2016;19(9):860–9.PubMedCrossRef
23.
Yang M, et al. The natural compound sulforaphene, as a novel anticancer reagent, targeting PI3K–AKT signaling pathway in lung cancer. Oncotarget. 2016;7(47):76656–66.PubMedPubMedCentral
24.
Yang M, et al. Sulforaphene inhibits triple negative breast cancer through activating tumor suppressor Egr1. Breast Cancer Res Treat. 2016;158(2):277–86.PubMedCrossRef
25.
Mondal A, et al. Sulforaphene promotes Bax/Bcl2, MAPK-dependent human gastric cancer AGS cells apoptosis and inhibits migration via EGFR, p-ERK1/2 down-regulation. Gen Physiol Biophys. 2016;35(1):25–34.PubMed
26.
Byun S, et al. Sulforaphene suppresses growth of colon cancer-derived tumors via induction of glutathione depletion and microtubule depolymerization. Mol Nutr Food Res. 2016;60(5):1068–78.PubMedCrossRef
27.
Deak M, et al. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO J. 1998;17(15):4426–41.PubMedPubMedCentralCrossRef
28.
29.
Wiggin GR, et al. MSK1 and MSK2 are required for the mitogen- and stress-induced phosphorylation of CREB and ATF1 in fibroblasts. Mol Cell Biol. 2002;22(8):2871–81.PubMedPubMedCentralCrossRef
30.
Czabotar PE, et al. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15(1):49–63.PubMedCrossRef
31.
Kntayya SB, et al. Induction of apoptosis and cytotoxicity by isothiocyanate sulforaphene in human hepatocarcinoma HepG2 cells. Nutrients. 2018;10(6):718.PubMedCentralCrossRef
32.
Smith A, et al. Imidazo[1,2-a]pyridin-6-yl-benzamide analogs as potent RAF inhibitors. Bioorg Med Chem Lett. 2017;27(23):5221–4.PubMedCrossRef
33.
Alessio N, et al. Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process. Oncotarget. 2015;6(10):8155–66.PubMedCrossRef
Metadata
Title
Sulforaphene induces apoptosis and inhibits the invasion of esophageal cancer cells through MSK2/CREB/Bcl-2 and cadherin pathway in vivo and in vitro
Authors
Chengjuan Zhang
Junxia Zhang
Qiong Wu
Benling Xu
Guoguo Jin
Yan Qiao
Simin Zhao
Yang Yang
Jinwen Shang
Xiaofang Li
Kangdong Liu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-1061-1

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue

Primary research

Expression of the Wnt ligands gene family and its relationship to prognosis in hepatocellular carcinoma

Primary research

KCNQ1OT1 aggravates cell proliferation and migration in bladder cancer through modulating miR-145-5p/PCBP2 axis

Primary research

Over-expression of Nectin-4 promotes progression of esophageal cancer and correlates with poor prognosis of the patients

Primary research

Amphicrine carcinoma of the stomach and intestine: a clinicopathologic and pan-cancer transcriptome analysis of a distinct entity

Primary research

Monocarboxylate transporter 1 and monocarboxylate transporter 4 in cancer-endothelial co-culturing microenvironments promote proliferation, migration, and invasion of renal cancer cells

Primary research

Identification of hub genes and therapeutic drugs in esophageal squamous cell carcinoma based on integrated bioinformatics strategy
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