Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells

Simona Martinotti; Elia Ranzato; Monica Parodi; Massimo Vitale; Bruno Burlando

doi:10.1016/j.taap.2013.10.025

Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells

Simona Martinotti, Elia Ranzato, Monica Parodi, Massimo Vitale, Bruno Burlando

Department of Science and Technological Innovation

Research output: Contribution to journal › Article › peer-review

Abstract

Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca²⁺, annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment.

Original language	English
Pages (from-to)	35-41
Number of pages	7
Journal	Toxicology and Applied Pharmacology
Volume	274
Issue number	1
DOIs	https://doi.org/10.1016/j.taap.2013.10.025
Publication status	Published - 1 Jan 2014

Keywords

Cell cycle
Combined therapy
DAPK2
PCR array
REN mesothelioma cells

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10.1016/j.taap.2013.10.025

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title = "Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells",

abstract = "Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca2+, annexin V, and DNA content. StellArray{\texttrademark} PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment.",

keywords = "Cell cycle, Combined therapy, DAPK2, PCR array, REN mesothelioma cells",

author = "Simona Martinotti and Elia Ranzato and Monica Parodi and Massimo Vitale and Bruno Burlando",

note = "Funding Information: This work was supported by Fondazione Buzzi Unicem (Casale Monferrato, Italy) , grant no. FBU-P27 . ",

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doi = "10.1016/j.taap.2013.10.025",

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T1 - Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells

AU - Martinotti, Simona

AU - Ranzato, Elia

AU - Parodi, Monica

AU - Vitale, Massimo

AU - Burlando, Bruno

N1 - Funding Information: This work was supported by Fondazione Buzzi Unicem (Casale Monferrato, Italy) , grant no. FBU-P27 .

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca2+, annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment.

AB - Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca2+, annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment.

KW - Cell cycle

KW - Combined therapy

KW - DAPK2

KW - PCR array

KW - REN mesothelioma cells

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DO - 10.1016/j.taap.2013.10.025

M3 - Article

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JO - Toxicology and Applied Pharmacology

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ER -

Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells

Abstract

Keywords

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