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
Tumor Biology
Published in: Tumor Biology 2/2016

01-02-2016 | Original Article

Fangchinoline suppresses the growth and invasion of human glioblastoma cells by inhibiting the kinase activity of Akt and Akt-mediated signaling cascades

Authors: Bingyu Guo, Peng Xie, Jingyuan Su, Tingting Zhang, Xiaoming Li, Guobiao Liang

Published in: Tumor Biology | Issue 2/2016

Login to get access

Abstract

Glioblastoma multiforme (GBM) is one of the most palindromic and malignant central nervous system neoplasms, and the current treatment is not effectual for GBM. Research of specific medicine for GBM is significant. Fangchinoline possesses a wide range of pharmacological activities and attracts more attentions due to its anti-tumor effects. In this study, two WHO grade IV human GBM cell lines (U87 MG and U118 MG) were exposed to fangchinoline, and we found that fangchinoline specifically inhibits the kinase activity of Akt and markedly suppresses the phosphorylation of Thr308 and Ser473 of Akt in human GBM cells. We also observed that fangchinoline inhibits tumor cell proliferation and invasiveness and induces apoptosis through suppressing the Akt-mediated signaling cascades, including Akt/p21, Akt/Bad, and Akt/matrix metalloproteinases (MMPs). These data demonstrated that fangchinoline exerts its anti-tumor effects in human glioblastoma cells, at least partly by inhibiting the kinase activity of Akt and suppressing Akt-mediated signaling cascades.
Literature
1.
Ahmed KA, Chinnaiyan P. Applying metabolomics to understand the aggressive phenotype and identify novel therapeutic targets in glioblastoma. Metabolites. 2014;4:740–50.CrossRefPubMedPubMedCentral
2.
Agrawal NS, Miller R, Jr., Lal R, Mahanti H, Dixon-Mah YN, DeCandio ML, et al. Current studies of immunotherapy on glioblastoma. J Neurol Neurosurg. 2014;5:1(1).
3.
Kazlauskas A, Cooper JA. Phosphorylation of the PDGF receptor beta subunit creates a tight binding site for phosphatidylinositol 3 kinase. EMBO J. 1990;9:3279–86.PubMedPubMedCentral
4.
Chiang EP, Tsai SY, Kuo YH, Pai MH, Chiu HL, Rodriguez RL, et al. Caffeic acid derivatives inhibit the growth of colon cancer: involvement of the PI3-K/Akt and AMPK signaling pathways. PloS one. 2014;9:e99631.CrossRefPubMedPubMedCentral
5.
Gustin JP, Karakas B, Weiss MB, Abukhdeir AM, Lauring J, Garay JP, et al. Knockin of mutant pik3ca activates multiple oncogenic pathways. Proc Natl Acad Sci U S A. 2009;106:2835–40.CrossRefPubMedPubMedCentral
6.
Kang S, Bader AG, Vogt PK. Phosphatidylinositol 3-kinase mutations identified in human cancer are oncogenic. Proc Natl Acad Sci U S A. 2005;102:802–7.CrossRefPubMedPubMedCentral
7.
Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, et al. High frequency of mutations of the pik3ca gene in human cancers. Science. 2004;304:554.CrossRefPubMed
8.
Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 2006;6:184–92.CrossRefPubMed
9.
10.
McDowell KA, Riggins GJ, Gallia GL. Targeting the Akt pathway in glioblastoma. Curr Pharm Des. 2011;17:2411–20.CrossRefPubMed
11.
Suzuki Y, Shirai K, Oka K, Mobaraki A, Yoshida Y, Noda SE, et al. Higher pAkt expression predicts a significant worse prognosis in glioblastomas. J Radiat Res. 2010;51:343–8.CrossRefPubMed
12.
13.
Wang Y, Chen J, Wang L, Huang Y, Leng Y, Wang G. Fangchinoline induces G0/G1 arrest by modulating the expression of CDKN1A and CCND2 in K562 human chronic myelogenous leukemia cells. Exp Ther Med. 2013;5:1105–12.PubMedPubMedCentral
14.
Wang CD, Yuan CF, Bu YQ, Wu XM, Wan JY, Zhang L, et al. Fangchinoline inhibits cell proliferation via Akt/gsk-3beta/cyclin d1 signaling and induces apoptosis in MDA-MB-231 breast cancer cells. Asian Pac J Cancer Prev. 2014;15:769–73.CrossRefPubMed
15.
Wang N, Pan W, Zhu M, Zhang M, Hao X, Liang G, et al. Fangchinoline induces autophagic cell death via p53/sestrin2/AMPK signalling in human hepatocellular carcinoma cells. Br J Pharmacol. 2011;164:731–42.CrossRefPubMedPubMedCentral
16.
Wang CD, Huang JG, Gao X, Li Y, Zhou SY, Yan X, et al. Fangchinoline induced G1/S arrest by modulating expression of p27, PCNA, and cyclin D in human prostate carcinoma cancer PC3 cells and tumor xenograft. Biosci Biotechnol Biochem. 2010;74:488–93.CrossRefPubMed
17.
Guo B, Su J, Zhang T, Wang K, Li X. Fangchinoline as a kinase inhibitor targets FAK and suppresses FAK-mediated signaling pathway in A549. J Drug Target. 2015;23:266–74.CrossRefPubMed
18.
Zhang YH, Fang LH, Ku BS. Fangchinoline inhibits rat aortic vascular smooth muscle cell proliferation and cell cycle progression through inhibition of ERK1/2 activation and c-fos expression. Biochem Pharmacol. 2003;66:1853–60.CrossRefPubMed
19.
Meng LH, Zhang H, Hayward L, Takemura H, Shao RG, Pommier Y. Tetrandrine induces early G1 arrest in human colon carcinoma cells by down-regulating the activity and inducing the degradation of G1-S-specific cyclin-dependent kinases and by inducing p53 and p21Cip1. Cancer Res. 2004;64:9086–92.CrossRefPubMed
20.
Sun X, Xu R, Deng Y, Cheng H, Ma J, Ji J, et al. Effects of tetrandrine on apoptosis and radiosensitivity of nasopharyngeal carcinoma cell line CNE. Acta Biochim Biophys Sin. 2007;39:869–78.CrossRefPubMed
21.
Xing Z, Zhang Y, Zhang X, Yang Y, Ma Y, Pang D. Fangchinoline induces G1 arrest in breast cancer cells through cell-cycle regulation. Phytother Res. 2013;27:1790–4.CrossRefPubMed
22.
Xing ZB, Yao L, Zhang GQ, Zhang XY, Zhang YX, Pang D. Fangchinoline inhibits breast adenocarcinoma proliferation by inducing apoptosis. Chem Pharm Bull. 2011;59:1476–80.CrossRefPubMed
23.
Baki A, Bielik A, Molnar L, Szendrei G, Keseru GM. A high throughput luminescent assay for glycogen synthase kinase-3beta inhibitors. Assay Drug Dev Technol. 2007;5:75–83.CrossRefPubMed
24.
25.
Tian F, Ding D, Li D. Fangchinoline targets PI3K and suppresses PI3K/Akt signaling pathway in SGC7901 cells. Int J Oncol. 2015;46:2355–63.PubMedPubMedCentral
26.
Chautard E, Ouedraogo ZG, Biau J, Verrelle P. Role of Akt in human malignant glioma: from oncogenesis to tumor aggressiveness. J Neurooncol. 2014;117:205–15.CrossRefPubMed
27.
Sonoda Y, Ozawa T, Aldape KD, Deen DF, Berger MS, Pieper RO. Akt pathway activation converts anaplastic astrocytoma to glioblastoma multiforme in a human astrocyte model of glioma. Cancer Res. 2001;61:6674–8.PubMed
28.
Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal. 2002;14:381–95.CrossRefPubMed
29.
Metadata
Title
Fangchinoline suppresses the growth and invasion of human glioblastoma cells by inhibiting the kinase activity of Akt and Akt-mediated signaling cascades
Authors
Bingyu Guo
Peng Xie
Jingyuan Su
Tingting Zhang
Xiaoming Li
Guobiao Liang
Publication date
01-02-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3990-1

Other articles of this Issue 2/2016

Tumor Biology 2/2016 Go to the issue

Original Article

Tumor necrosis factor superfamily member 13 is a novel biomarker for diagnosis and prognosis and promotes cancer cell proliferation in laryngeal squamous cell carcinoma

Original Article

An orally administered DNA vaccine targeting vascular endothelial growth factor receptor-3 inhibits lung carcinoma growth

Original Article

Circulating CD105 shows significant impact in patients of oral cancer and promotes malignancy of cancer cells via CCL20

Original Article

Diagnostic significance of S100A2 and S100A6 levels in sera of patients with non-small cell lung cancer

Original Article

The R156R ERCC2 polymorphism as a risk factor of endometrial cancer

Original Article

Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity
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