Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells
Joint Authors
Rasul, Azhar
Khan, Muhammad
Yang, Hong
Zheng, Bin
Yi, Fei
Gu, Zhuyi
Li, Ting
Gao, Hongwen
Qazi, Javed Iqbal
Ma, Tonghui
Source
Evidence-Based Complementary and Alternative Medicine
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-06-20
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Pseudolaric acid B (PLAB) is one of the major bioactive components of Pseudolarix kaempferi.
It has been reported to exhibit inhibitory effect on cell proliferation in several types of cancer cells.
However, there is no report elucidating its effect on glioma cells and organ toxicity in vivo.
In the present study, we found that PLAB inhibited growth of U87 glioblastoma cells in a dose-dependent manner with IC50~10 μM.
Flow cytometry analysis showed that apoptotic cell death mediated by PLAB was accompanied with cell cycle arrest at G2/M phase.
Using Western blot, we found that PLAB induced G2/M phase arrest by inhibiting tubulin polymerization in U87 cells.
Apoptotic cell death was only partially inhibited by pancaspase inhibitor, z-VAD-fmk, which suggested that PLAB-induced apoptosis in U87 cells is partially caspase-independent.
Further mechanistic study demonstrated that PLAB induced caspase-dependent apoptosis via upregulation of p53, increased level of proapoptotic protein Bax, decreased level of antiapoptotic protein Bcl-2, release of cytochrome c from mitochondria, activation of caspase-3 and proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-independent apoptosis through apoptosis inducing factor (AIF).
Furthermore, in vivo toxicity study demonstrated that PLAB did not induce significant structural and biochemical changes in mouse liver and kidneys at a dose of 25 mg/kg.
Therefore, PLAB may become a potential lead compound for future development of antiglioma therapy.
American Psychological Association (APA)
Khan, Muhammad& Zheng, Bin& Yi, Fei& Rasul, Azhar& Gu, Zhuyi& Li, Ting…[et al.]. 2012. Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells. Evidence-Based Complementary and Alternative Medicine،Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-1028651
Modern Language Association (MLA)
Khan, Muhammad…[et al.]. Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells. Evidence-Based Complementary and Alternative Medicine No. 2012 (2012), pp.1-11.
https://search.emarefa.net/detail/BIM-1028651
American Medical Association (AMA)
Khan, Muhammad& Zheng, Bin& Yi, Fei& Rasul, Azhar& Gu, Zhuyi& Li, Ting…[et al.]. Pseudolaric Acid B Induces Caspase-Dependent and Caspase-Independent Apoptosis in U87 Glioblastoma Cells. Evidence-Based Complementary and Alternative Medicine. 2012. Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-1028651
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1028651