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
Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 3/2016

01-03-2016 | Research Article

XIAP inhibitor Embelin inhibits bladder cancer survival and invasion in vitro

Authors: X. Fu, X. Pang, H. Qi, S. Chen, Y. Li, W. Tan

Published in: Clinical and Translational Oncology | Issue 3/2016

Login to get access

Abstract

Background

Bladder cancer is the second most common urological malignancy around the world and is by far the most frequent urological malignancy in China. Embelin is an active compound identified as a novel X-chromosome-linked IAP (XIAP) inhibitor from the Embelia ribes that exhibits various medicinal effects including anti-inflammatory and anti-cancer activities. However, therapeutic effect of Embelin to human bladder cancer is not yet determined.

Methods

We evaluated the sensitizing potential of Embelin on inhibiting cell growth and migration of bladder cancer cell line by CCK8, Transwell, and Western Blot, and explored its related mechanism. We performed IHC staining of XIAP in 35 bladder cancer tissues and corresponding adjacent non-neoplastic tissues.

Results

XIAP was significantly upregulated in bladder cancer cases. When the concentration of Embelin was used respectively at 5, 10, 20, 25, and 35 µmol/l, the survival of both T24 and 5637 cells decreased in a dose-/time-dependent manner. Our study confirmed that with the increase of concentration of Embelin, the expression levels of PI3K and p-Akt decreased significantly which further confirmed that Embelin inhibits cell growth by inducing apoptosis via PI3K/Akt pathway.

Conclusions

Embelin may be developed into a novel and potential chemotherapeutic drug for bladder cancer.
Literature
1.
2.
Witjes JA, Comperat E, Cowan NC, De Santis M, Gakis G, Lebret T, et al. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol. 2014;65(4):778–92.CrossRefPubMed
3.
Von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602–8.CrossRefPubMed
4.
5.
Garcia-Fernandez M, Kissel H, Brown S, Gorenc T, Schile AJ, Rafii S, et al. Sept4/arts is required for stem cell apoptosis and tumor suppression. Genes Dev. 2010;24(20):2282–93.PubMedCentralCrossRefPubMed
6.
Debatin KM. Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immunother. 2004;53(3):153–9.CrossRefPubMed
7.
Joshi R, Kamat JP, Mukherjee T. Free radical scavenging reactions and antioxidant activity of embelin: biochemical and pulse radiolytic studies. Chem Biol Interact. 2007;167(2):125–34.CrossRefPubMed
8.
9.
Yang T, Lan J, Huang Q, Chen X, Sun X, Liu X, et al. Embelin sensitizes acute myeloid leukemia cells to TRAIL through XIAP inhibition and NF-κB inactivation. Cell Biochem Biophys. 2015;71(1):291–7.CrossRefPubMed
10.
Waerner T, Alacakaptan M, Tamir I, Oberauer R, Gal A, Brabletz T, et al. ILEI: a cytokine essential for EMT, tumor formation, and late events in metastasis in epithelial cells. Cancer Cell. 2006;10(3):227–39.CrossRefPubMed
11.
Beug ST, LaCasse EC, Korneluk RG. Smac mimetics combined with innate immune stimuli create the perfect cytokine storm to kill tumor cells. Oncoimmunology. 2014;3:e28541.PubMedCentralCrossRefPubMed
12.
Yabal M, Muller N, Adler H, Knies N, Gross CJ, Damgaard RB, et al. Xiap restricts tnf- and rip3-dependent cell death and inflammasome activation. Cell Rep. 2014;7(6):1796–808.CrossRefPubMed
13.
Paschall AV, Zimmerman MA, Torres CM, Yang D, Chen MR, Li X, et al. Ceramide targets xiap and ciap1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression. BMC Cancer. 2014;14:24.PubMedCentralCrossRefPubMed
14.
Moreno-Martinez D, Nomdedeu M, Lara-Castillo MC, Etxabe A, Pratcorona M, Tesi N, et al. Xiap inhibitors induce differentiation and impair clonogenic capacity of acute myeloid leukemia stem cells. Oncotarget. 2014;5(12):4337–46.PubMedCentralCrossRefPubMed
15.
Shi Y. Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell. 2002;9(3):459–70.CrossRefPubMed
16.
Li X, Huang T, Jiang G, Gong W, Qian H, Zou C. Synergistic apoptotic effect of crocin and cisplatin on osteosarcoma cells via caspase induced apoptosis. Toxicol Lett. 2013;221(3):197–204.CrossRefPubMed
Metadata
Title
XIAP inhibitor Embelin inhibits bladder cancer survival and invasion in vitro
Authors
X. Fu
X. Pang
H. Qi
S. Chen
Y. Li
W. Tan
Publication date
01-03-2016
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 3/2016
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-015-1363-2

Other articles of this Issue 3/2016

Clinical and Translational Oncology 3/2016 Go to the issue

Research Article

Shorter hemodialysis duration is a risk factor for the recurrence of urothelial carcinoma of the bladder in patients on maintenance hemodialysis

Review Article

Central nervous system niche involvement in the leukemia

Review Article

Tumor-associated macrophages in cancers

Research Article

Stereotactic body radiotherapy (SBRT) for the treatment of inoperable stage I non-small cell lung cancer patients

Research Article

Methylation of ASC/TMS1 promoter is associated with poor prognosis of patients with gastric cancer

Review Article

The role of human epididymis protein 4 in the diagnosis of epithelial ovarian 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