Hypoxia enhances cytotoxicity of wedelolactone to breast cancer
cells

a 2014

Hypoxia enhances cytotoxicity of wedelolactone to breast cancer cells

BENEŠ, Petr, Tereza NEHYBOVÁ, Lucia KNOPFOVÁ and Jan ŠMARDA

Basic information

Original name

Hypoxia enhances cytotoxicity of wedelolactone to breast cancer cells

Authors

BENEŠ, Petr, Tereza NEHYBOVÁ, Lucia KNOPFOVÁ and Jan ŠMARDA

Edition

3rd International Conference on Tumor Microenvironment and Cellular Stress, Mykonos, Greece. 2014

Other information

Type of outcome

Konferenční abstrakt

Confidentiality degree

není předmětem státního či obchodního tajemství

Změněno: 6/1/2015 10:37, doc. Mgr. Petr Beneš, Ph.D.

Abstract

V originále

Microenvironment of solid tumors is characterized by hypoxia as a result of malformed vasculature and inadequate perfusion. Tumor cells, however, developed various strategies to adapt to hypoxic microenvironment. Numerous studies reported link between severe hypoxia and cancer progression. Nevertheless, recent studies have shown that hypoxia can affect the effectiveness of chemotherapy as well. Wedelolactone is a plant polyphenolic coumestan with in vitro and in vivo anti-cancer properties. Many proteins and signaling pathways were identified as wedelolactone targets including NFkB, steroid receptors, MAPK kinases and topoisomerase II. We have demonstrated that induction of oxidative stress represent another mechanism of its cytotoxicity. This study was designed to analyze the modulatory effect of hypoxia to cytotoxicity of wedelolactone to MDA-MB-231 and T47D breast cancer cells. We observed that hypoxia significantly enhanced pro-apoptotic effect of wedelolactone in both cell lines as documented by analysis of nuclear morphology, PARP cleavage and phosphatidylserine externalization. The enhancing effect of hypoxia was associated with altered ROS kinetics and stress signaling response. We believe that cytotoxicity of newly developed/tested chemotherapeutics in conditions of specific tumor microenvironment has to be considered in their pre-clinical studies.

Links

CZ.1.07/2.3.00/20.0183, interní kód MU

Name: Centrum experimentální biomedicíny (Acronym: CEB)

Investor: Ministry of Education, Youth and Sports of the CR, 2.3 Human resources in research and development

NT13441, research and development project

Name: Exprese proteinů rodiny Myb v adenokarcinomech tlustého střeva a vztah k jejich metastatickému potenciálu

Citovat

BENEŠ, Petr, Tereza NEHYBOVÁ, Lucia KNOPFOVÁ and Jan ŠMARDA. Hypoxia enhances cytotoxicity of wedelolactone to breast cancer cells. In 3rd International Conference on Tumor Microenvironment and Cellular Stress, Mykonos, Greece. 2014.

@proceedings{1214984,
   author = {Beneš, Petr and Nehybová, Tereza and Knopfová, Lucia and Šmarda, Jan},
   booktitle = {3rd International Conference on Tumor Microenvironment and Cellular Stress, Mykonos, Greece.},
   title = {Hypoxia enhances cytotoxicity of wedelolactone to breast cancer cells},
   year = {2014}
}

TY  - CONF
ID  - 1214984
AU  - Beneš, Petr - Nehybová, Tereza - Knopfová, Lucia - Šmarda, Jan
PY  - 2014
TI  - Hypoxia enhances cytotoxicity of wedelolactone to breast cancer cells
N2  - Microenvironment of solid tumors is characterized by hypoxia as a result of malformed vasculature and inadequate perfusion. Tumor cells, however, developed various strategies to adapt to hypoxic microenvironment. Numerous studies reported link between severe hypoxia and cancer progression. Nevertheless, recent studies have shown that hypoxia can affect the effectiveness of chemotherapy as well. Wedelolactone is a plant polyphenolic coumestan with in vitro and in vivo anti-cancer properties. Many proteins and signaling pathways were identified as wedelolactone targets including NFkB, steroid receptors, MAPK kinases and topoisomerase II. We have demonstrated that induction of oxidative stress represent another mechanism of its cytotoxicity. This study was designed to analyze the modulatory effect of hypoxia to cytotoxicity of wedelolactone to MDA-MB-231 and T47D breast cancer cells. We observed that hypoxia significantly enhanced pro-apoptotic effect of wedelolactone in both cell lines as documented by analysis of nuclear morphology, PARP cleavage and phosphatidylserine externalization. The enhancing effect of hypoxia was associated with altered ROS kinetics and stress signaling response. We believe that cytotoxicity of newly developed/tested chemotherapeutics in conditions of specific tumor microenvironment has to be considered in their pre-clinical studies.
ER  -

BENEŠ, Petr, Tereza NEHYBOVÁ, Lucia KNOPFOVÁ and Jan ŠMARDA. Hypoxia enhances cytotoxicity of wedelolactone to breast cancer cells. In \textit{3rd International Conference on Tumor Microenvironment and Cellular Stress, Mykonos, Greece.}. 2014.

Detailed Information on Publication Record