Valproic acid increases the in vitro effects of nitrosureas on human glioma cell lines

Emilio Ciusani, Marco Balzarotti, Chiara Calatozzolo, Ugo De Grazia, Amerigo Boiardi, Andrea Salmaggi, Danilo Croci

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Valproic acid (VPA) has been recently investigated for its anticancer properties in different tumors, including malignant gliomas. The aim of the present work was to evaluate the effects of VPA, alone or in combination with other chemotherapeutic drugs, on in vitro growth of human glioma cell lines. A172, U373, U138, U87, and SW1783 were treated with VPA alone or in combination with mitoxantrone, etoposide, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The effects of treatments on cell growth were assessed with crystal violet staining and analyzed using the combination index (CI). The percentage of apoptotic cells and the DNA content for cell cycle phases detection were also investigated by flow cytometry. Despite a certain variability, glioma cell lines were rather resistant to the drugs tested. Addition of VPA decreased the IC50 of the chemotherapeutic agents in all cell lines tested. This effect was more evident with BCNU. The synergic effect of the association of VPA and BCNU was related to an increased block of cell cycle with accumulation in S-G2/M phases of cell cycle rather than an increased programmed cell death. In our experimental model, VPA showed anticancer properties per se on human glioma cell lines and our data support the hypothesis that, if used in association with conventional chemotherapy, it might improve the effects of single chemotherapeutic agents.

Original languageEnglish
Pages (from-to)453-463
Number of pages11
JournalOncology Research
Volume16
Issue number10
DOIs
Publication statusPublished - 2007

Fingerprint

Valproic Acid
Glioma
Carmustine
Cell Line
Cell Cycle
Gentian Violet
Mitoxantrone
G2 Phase
Etoposide
Growth
Pharmaceutical Preparations
Cell Division
Inhibitory Concentration 50
In Vitro Techniques
Flow Cytometry
Cell Death
Theoretical Models
Staining and Labeling
Drug Therapy
DNA

Keywords

  • Apoptosis
  • BCNU
  • Cell cycle
  • Glioma
  • Histone deacetylase
  • Valproic acid

ASJC Scopus subject areas

  • Cancer Research

Cite this

Valproic acid increases the in vitro effects of nitrosureas on human glioma cell lines. / Ciusani, Emilio; Balzarotti, Marco; Calatozzolo, Chiara; De Grazia, Ugo; Boiardi, Amerigo; Salmaggi, Andrea; Croci, Danilo.

In: Oncology Research, Vol. 16, No. 10, 2007, p. 453-463.

Research output: Contribution to journalArticle

Ciusani, Emilio ; Balzarotti, Marco ; Calatozzolo, Chiara ; De Grazia, Ugo ; Boiardi, Amerigo ; Salmaggi, Andrea ; Croci, Danilo. / Valproic acid increases the in vitro effects of nitrosureas on human glioma cell lines. In: Oncology Research. 2007 ; Vol. 16, No. 10. pp. 453-463.
@article{97eb0eb03f2b4676bbc56a0a47b8b6e8,
title = "Valproic acid increases the in vitro effects of nitrosureas on human glioma cell lines",
abstract = "Valproic acid (VPA) has been recently investigated for its anticancer properties in different tumors, including malignant gliomas. The aim of the present work was to evaluate the effects of VPA, alone or in combination with other chemotherapeutic drugs, on in vitro growth of human glioma cell lines. A172, U373, U138, U87, and SW1783 were treated with VPA alone or in combination with mitoxantrone, etoposide, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The effects of treatments on cell growth were assessed with crystal violet staining and analyzed using the combination index (CI). The percentage of apoptotic cells and the DNA content for cell cycle phases detection were also investigated by flow cytometry. Despite a certain variability, glioma cell lines were rather resistant to the drugs tested. Addition of VPA decreased the IC50 of the chemotherapeutic agents in all cell lines tested. This effect was more evident with BCNU. The synergic effect of the association of VPA and BCNU was related to an increased block of cell cycle with accumulation in S-G2/M phases of cell cycle rather than an increased programmed cell death. In our experimental model, VPA showed anticancer properties per se on human glioma cell lines and our data support the hypothesis that, if used in association with conventional chemotherapy, it might improve the effects of single chemotherapeutic agents.",
keywords = "Apoptosis, BCNU, Cell cycle, Glioma, Histone deacetylase, Valproic acid",
author = "Emilio Ciusani and Marco Balzarotti and Chiara Calatozzolo and {De Grazia}, Ugo and Amerigo Boiardi and Andrea Salmaggi and Danilo Croci",
year = "2007",
doi = "10.3727/096504007783338340",
language = "English",
volume = "16",
pages = "453--463",
journal = "Oncology Research",
issn = "0965-0407",
publisher = "Cognizant Communication Corporation",
number = "10",

}

TY - JOUR

T1 - Valproic acid increases the in vitro effects of nitrosureas on human glioma cell lines

AU - Ciusani, Emilio

AU - Balzarotti, Marco

AU - Calatozzolo, Chiara

AU - De Grazia, Ugo

AU - Boiardi, Amerigo

AU - Salmaggi, Andrea

AU - Croci, Danilo

PY - 2007

Y1 - 2007

N2 - Valproic acid (VPA) has been recently investigated for its anticancer properties in different tumors, including malignant gliomas. The aim of the present work was to evaluate the effects of VPA, alone or in combination with other chemotherapeutic drugs, on in vitro growth of human glioma cell lines. A172, U373, U138, U87, and SW1783 were treated with VPA alone or in combination with mitoxantrone, etoposide, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The effects of treatments on cell growth were assessed with crystal violet staining and analyzed using the combination index (CI). The percentage of apoptotic cells and the DNA content for cell cycle phases detection were also investigated by flow cytometry. Despite a certain variability, glioma cell lines were rather resistant to the drugs tested. Addition of VPA decreased the IC50 of the chemotherapeutic agents in all cell lines tested. This effect was more evident with BCNU. The synergic effect of the association of VPA and BCNU was related to an increased block of cell cycle with accumulation in S-G2/M phases of cell cycle rather than an increased programmed cell death. In our experimental model, VPA showed anticancer properties per se on human glioma cell lines and our data support the hypothesis that, if used in association with conventional chemotherapy, it might improve the effects of single chemotherapeutic agents.

AB - Valproic acid (VPA) has been recently investigated for its anticancer properties in different tumors, including malignant gliomas. The aim of the present work was to evaluate the effects of VPA, alone or in combination with other chemotherapeutic drugs, on in vitro growth of human glioma cell lines. A172, U373, U138, U87, and SW1783 were treated with VPA alone or in combination with mitoxantrone, etoposide, or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The effects of treatments on cell growth were assessed with crystal violet staining and analyzed using the combination index (CI). The percentage of apoptotic cells and the DNA content for cell cycle phases detection were also investigated by flow cytometry. Despite a certain variability, glioma cell lines were rather resistant to the drugs tested. Addition of VPA decreased the IC50 of the chemotherapeutic agents in all cell lines tested. This effect was more evident with BCNU. The synergic effect of the association of VPA and BCNU was related to an increased block of cell cycle with accumulation in S-G2/M phases of cell cycle rather than an increased programmed cell death. In our experimental model, VPA showed anticancer properties per se on human glioma cell lines and our data support the hypothesis that, if used in association with conventional chemotherapy, it might improve the effects of single chemotherapeutic agents.

KW - Apoptosis

KW - BCNU

KW - Cell cycle

KW - Glioma

KW - Histone deacetylase

KW - Valproic acid

UR - http://www.scopus.com/inward/record.url?scp=38149069545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38149069545&partnerID=8YFLogxK

U2 - 10.3727/096504007783338340

DO - 10.3727/096504007783338340

M3 - Article

VL - 16

SP - 453

EP - 463

JO - Oncology Research

JF - Oncology Research

SN - 0965-0407

IS - 10

ER -