Valproic Acid Downregulates the Expression of MGMT and Sensitizes Temozolomide-Resistant Glioma Cells
Joint Authors
Kim, Seong Muk
Hou, Yun
Park, Kwang Ywel
Ryu, Chung Heon
Lim, Jung Yeon
Yoon, Wan Soo
Jeong, Chang Hyun
Jeun, Sin-Soo
Woo, Ji Sun
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-06-04
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Temozolomide (TMZ) has become a key therapeutic agent in patients with malignant gliomas; however, its survival benefit remains unsatisfactory.
Valproic acid (VPA) has emerged as an anticancer drug via inhibition of histone deacetylases (HDACs), but the therapeutic advantages of a combination with VPA and TMZ remain poorly understood.
The main aim of the present study was to determine whether an antitumor effect could be potentiated by a combination of VPA and TMZ, especially in TMZ-resistant cell lines.
A combination of VPA and TMZ had a significantly enhanced antitumor effect in TMZ-resistant malignant glioma cells (T98 and U138).
This enhanced antitumor effect correlated with VPA-mediated reduced O6-methylguanine-DNA methyltransferase (MGMT) expression, which plays an important role in cellular resistance to alkylating agents.
In vitro, the combination of these drugs enhanced the apoptotic and autophagic cell death, as well as suppressed the migratory activities in TMZ-resistant cell lines.
Furthermore, in vivo efficacy experiment showed that treatment of combination of VPA and TMZ significantly inhibited tumor growth compared with the monotherapy groups of mice.
These results suggest that the clinical efficacy of TMZ chemotherapy in TMZ-resistant malignant glioma may be improved by combination with VPA.
American Psychological Association (APA)
Ryu, Chung Heon& Yoon, Wan Soo& Park, Kwang Ywel& Kim, Seong Muk& Lim, Jung Yeon& Woo, Ji Sun…[et al.]. 2012. Valproic Acid Downregulates the Expression of MGMT and Sensitizes Temozolomide-Resistant Glioma Cells. BioMed Research International،Vol. 2012, no. 2012, pp.1-9.
https://search.emarefa.net/detail/BIM-991988
Modern Language Association (MLA)
Ryu, Chung Heon…[et al.]. Valproic Acid Downregulates the Expression of MGMT and Sensitizes Temozolomide-Resistant Glioma Cells. BioMed Research International No. 2012 (2012), pp.1-9.
https://search.emarefa.net/detail/BIM-991988
American Medical Association (AMA)
Ryu, Chung Heon& Yoon, Wan Soo& Park, Kwang Ywel& Kim, Seong Muk& Lim, Jung Yeon& Woo, Ji Sun…[et al.]. Valproic Acid Downregulates the Expression of MGMT and Sensitizes Temozolomide-Resistant Glioma Cells. BioMed Research International. 2012. Vol. 2012, no. 2012, pp.1-9.
https://search.emarefa.net/detail/BIM-991988
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-991988