The lignan, (-)-sesamin reveals cytotoxicity toward cancer cells: Pharmacogenomic determination of genes associated with sensitivity or resistance

Autoren

Mohamed Saeed
Hassan Khalid
Yoshikazu Sugimoto
Thomas Efferth

DOI

10.1016/j.phymed.2014.01.006

ISSN

0944-7113

Ausgabe der Veröffentlichung

5

Zeitschrift

Phytomedicine

Sprache

en

Paginierung

689 - 696

Datum der Veröffentlichung

2014

Status

Published

Herausgeber

Elsevier BV

Herausgeber URL

http://dx.doi.org/10.1016/j.phymed.2014.01.006

Datum der Datenerfassung

2020

Titel

The lignan, (−)-sesamin reveals cytotoxicity toward cancer cells: Pharmacogenomic determination of genes associated with sensitivity or resistance

Ausgabe der Zeitschrift

21

Data source: Crossref

Abstract

(-)-Sesamin is a lignan present in sesam oil and a number of medicinal plants. It exerts various pharmacological effects, such as prevention of hyperlipidemia, hypertension, and carcinogenesis. Moreover, (-)-sesamin has chemopreventive and anticancer activity in vitro and in vivo. Multidrug resistance (MDR) of tumors leads to fatal treatment outcome in many patients and novel drugs able to kill multidrug-resistant cells are urgently needed. P-glycoprotein (MDR1/ABCB1) is the best known ATP-binding cassette (ABC) drug transporter mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. We found that the mRNA expressions of ABCB1 and ABCB5 were not related to the 50% inhibition concentrations (IC50) for (-)-sesamin in a panel of 55 cell lines of the National Cancer Institute, USA. Furthermore, (-)-sesamin inhibited ABCB1- or ABCB5-overexpressing cells with similar efficacy than their drug-sensitive parental counterparts. In addition to ABC transporter-mediated MDR, we attempted to identify other molecular determinants of (-)-sesamin resistance. For this reason, we performed COMPARE and hierarchical cluster analyses of the transcriptome-wide microarray-based mRNA expression of the NCI cell panel. Twenty-three genes were identified, whose mRNA expression correlated with the IC50 values for (-)-sesamin. These genes code for proteins of different biological functions, i.e. ribosomal proteins, components of the mitochondrial respiratory chain, proteins involved in RNA metabolism, protein biosynthesis, or glucose and fatty acid metabolism. Subjecting this set of genes to cluster analysis showed that the cell lines were assembled in the resulting dendrogram according to their responsiveness to (-)-sesamin. In conclusion, (-)-sesamin is not involved in MDR mediated by ABCB1 or ABCB5 and may be valuable to bypass chemoresistance of refractory tumors. The microarray expression profile, which predicted sensitivity or resistance of tumor cells to (-)-sesamin consisted of genes, which do not belong to the classical resistance mechanisms to established anticancer drugs.

Addresses

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.

Autoren

Mohamed Saeed
Hassan Khalid
Yoshikazu Sugimoto
Thomas Efferth
Thomas Efferth

DOI

10.1016/j.phymed.2014.01.006

eISSN

1618-095X

Externe Identifier

PubMed Identifier: 24556122

Open access

false

ISSN

0944-7113

Ausgabe der Veröffentlichung

5

Zeitschrift

Phytomedicine : international journal of phytotherapy and phytopharmacology

Schlüsselwörter

Cell Line, Tumor
Humans
Neoplasms
Lignans
Dioxoles
Plant Extracts
Phytotherapy
Drug Screening Assays, Antitumor
Cluster Analysis
Gene Expression Profiling
Drug Resistance, Neoplasm
HEK293 Cells
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1

Sprache

eng

Medium

Print-Electronic

Online publication date

2014

Paginierung

689 - 696

Datum der Veröffentlichung

2014

Status

Published

Datum der Datenerfassung

2014

Titel

The lignan, (-)-sesamin reveals cytotoxicity toward cancer cells: pharmacogenomic determination of genes associated with sensitivity or resistance.

Sub types

Research Support, Non-U.S. Gov't
Journal Article

Ausgabe der Zeitschrift

21

Data source: Europe PubMed Central

Abstract

(-)-Sesamin is a lignan present in sesam oil and a number of medicinal plants. It exerts various pharmacological effects, such as prevention of hyperlipidemia, hypertension, and carcinogenesis. Moreover, (-)-sesamin has chemopreventive and anticancer activity in vitro and in vivo. Multidrug resistance (MDR) of tumors leads to fatal treatment outcome in many patients and novel drugs able to kill multidrug-resistant cells are urgently needed. P-glycoprotein (MDR1/ABCB1) is the best known ATP-binding cassette (ABC) drug transporter mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. We found that the mRNA expressions of ABCB1 and ABCB5 were not related to the 50% inhibition concentrations (IC50) for (-)-sesamin in a panel of 55 cell lines of the National Cancer Institute, USA. Furthermore, (-)-sesamin inhibited ABCB1- or ABCB5-overexpressing cells with similar efficacy than their drug-sensitive parental counterparts. In addition to ABC transporter-mediated MDR, we attempted to identify other molecular determinants of (-)-sesamin resistance. For this reason, we performed COMPARE and hierarchical cluster analyses of the transcriptome-wide microarray-based mRNA expression of the NCI cell panel. Twenty-three genes were identified, whose mRNA expression correlated with the IC50 values for (-)-sesamin. These genes code for proteins of different biological functions, i.e. ribosomal proteins, components of the mitochondrial respiratory chain, proteins involved in RNA metabolism, protein biosynthesis, or glucose and fatty acid metabolism. Subjecting this set of genes to cluster analysis showed that the cell lines were assembled in the resulting dendrogram according to their responsiveness to (-)-sesamin. In conclusion, (-)-sesamin is not involved in MDR mediated by ABCB1 or ABCB5 and may be valuable to bypass chemoresistance of refractory tumors. The microarray expression profile, which predicted sensitivity or resistance of tumor cells to (-)-sesamin consisted of genes, which do not belong to the classical resistance mechanisms to established anticancer drugs.

Date of acceptance

2014

Autoren

Mohamed Saeed
Hassan Khalid
Yoshikazu Sugimoto
Thomas Efferth

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/24556122

DOI

10.1016/j.phymed.2014.01.006

eISSN

1618-095X

Ausgabe der Veröffentlichung

5

Zeitschrift

Phytomedicine

Schlüsselwörter

ABC transporters
ABCB1
ABCB5
Chemotherapy
Lignan, (-)-sesamin
Multidrug resistance
Pharmacogenomics
Phytotherapy
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
Cell Line, Tumor
Cluster Analysis
Dioxoles
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Gene Expression Profiling
HEK293 Cells
Humans
Lignans
Neoplasms
Phytotherapy
Plant Extracts

Sprache

eng

Country

Germany

Paginierung

689 - 696

PII

S0944-7113(14)00028-2

Datum der Veröffentlichung

2014

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2014

Titel

The lignan, (-)-sesamin reveals cytotoxicity toward cancer cells: pharmacogenomic determination of genes associated with sensitivity or resistance.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

21

Data source: PubMed

The lignan, (-)-sesamin reveals cytotoxicity toward cancer cells: Pharmacogenomic determination of genes associated with sensitivity or resistance

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