Silibinin-induced glioma cell apoptosis by PI3K-mediated but Akt-independent downregulation of FoxM1 expression

European Journal of Pharmacology
Mingjie ZhangShaoyi Li

Abstract

The oncogenic transcription factor Forkhead box M1 (FoxM1) is overexpressed in many human tumors, including glioma. As a critical regulator of the cell cycle and apoptosis-related genes, FoxM1 is a potential therapeutic target against human malignant glioma. Silibinin, a flavonoid isolated from Silybum marianum, dose-dependently reduced glioma cell proliferation, promoted apoptosis, and downregulated FoxM1 expression. Knockdown of FoxM1 by small hairpin RNA (shRNA) transfection also promoted glioma cell apoptosis and augmented the antiproliferative and pro-apoptotic properties of silibinin. Moreover, silibinin increased caspase-3 activation, upregulated pro-apoptotic Bax, and suppressed anti-apoptotic Bcl-2 expression, effects enhanced by FoxM1 knockdown. Silibinin treatment suppressed U87 cell PI3K phospho-activation, and simultaneous silibinin exposure, FoxM1 knockdown, and PI3K inhibition additively increased U87 cell apoptosis. Furthermore, PI3K inhibition reduced FoxM1 expression. Akt activity was also suppressed by FoxM1 downregulation but Akt inhibition did not alter FoxM1 expression. Thus, silibinin likely inhibited glioma cell proliferation and induced apoptosis through inactivation of PI3K and FoxM1, leading to activa...Continue Reading

References

Mar 17, 2004·Cancer Treatment Reviews·Juan Angel Fresno VaraManuel González-Barón
Sep 20, 2005·Chemico-biological Interactions·Pei-Ni ChenShu-Chen Chu
Jul 10, 2007·Acta Neuropathologica·David N LouisPaul Kleihues
Oct 19, 2007·Nature Reviews. Cancer·Stephen S Myatt, Eric W-F Lam
Nov 21, 2007·Biological Chemistry·Inken Wierstra, Jürgen Alves
Feb 26, 2008·Nature Reviews. Cancer·Stephen S Myatt, Eric W-F Lam
Apr 9, 2008·Critical Reviews in Oncology/hematology·Alba A BrandesCharles Vecht
Mar 12, 2009·Molecular Cancer Therapeutics·Ursula B McGovernEric W-F Lam
Aug 22, 2009·The EMBO Journal·Hyun Jung ParkPradip Raychaudhuri
Dec 18, 2009·Anti-cancer Agents in Medicinal Chemistry·Catherine Wing Ying CheungDavid Lawrence Nicol
Jan 14, 2010·Molecular Cancer Research : MCR·Jimmy M-M KwokEric W-F Lam
Mar 31, 2010·Carcinogenesis·Huixin WangW Andrew Yeudall
Apr 1, 2010·Pharmaceutical Research·Zhiwei WangFazlul H Sarkar
Mar 30, 2011·Current Drug Targets·Miranda S C WilsonEric W-F Lam
Apr 20, 2011·Journal of Experimental & Clinical Cancer Research : CR·Ji C JeongKi H Kim
Apr 27, 2011·Molecular Cancer Therapeutics·Julie MillourEric W F Lam
Sep 29, 2011·International Journal of Molecular Sciences·Yakun GeWei Shi
Apr 13, 2013·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Xinxin YangJing Chen
Jun 19, 2013·The Journal of Biological Chemistry·Yuqi CaiTanya V Kalin
Jul 4, 2013·BMC Cancer·Mingo Ming Ho YungHextan Yuen-Sheung Ngan
Jul 25, 2013·Cancer Letters·David Sadava, Susan E Kane
Dec 12, 2013·Molecular Cancer·Ming QuanKeping Xie

❮ Previous
Next ❯

Citations

Nov 16, 2016·Scientific Reports·Ofir CohnDan Levy
Aug 4, 2018·Journal of Cellular and Molecular Medicine·Weihan WangZhifan Jia
May 28, 2019·Journal of Cellular Biochemistry·Yugang Yin, Chun Yang
Aug 9, 2017·Journal of Experimental & Clinical Cancer Research : CR·Xue ZhangHong-Hao Zhou
Sep 10, 2020·Fetal and Pediatric Pathology·Junzuo LiaoYun Liang
Jul 30, 2019·Frontiers in Pharmacology·Weixiao AnShousong Cao
Apr 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dominique DelmasVirginie Aires
Feb 24, 2018·Frontiers in Pharmacology·Xiaoying HouLi Sun
Feb 25, 2021·The American Journal of Chinese Medicine·Yun-Suk KwonSoyoung Kim
Aug 2, 2021·Cellular and Molecular Life Sciences : CMLS·Mariana MedeirosMaría Sol Brassesco
Oct 14, 2020·Journal of Agricultural and Food Chemistry·Xin WangShuai-Cheng Wu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.