Cytotoxicity of sesquiterpene alkaloids from Nuphar plants toward sensitive and drug-resistant cell lines

Abstract

<p>Thioalkaloids isolated from <italic>Nuphar</italic> plants showed cytotoxic effects on sensitive and resistant cancer cell lines.</p>

Autoren

Masashi Fukaya
Seikou Nakamura
Mohamed Elamir F Hegazy
Yoshikazu Sugimoto
Noriko Hayashi
Souichi Nakashima
Masayuki Yoshikawa
Thomas Efferth
Hisashi Matsuda

DOI

10.1039/c8fo01804a

eISSN

2042-650X

ISSN

2042-6496

Ausgabe der Veröffentlichung

12

Zeitschrift

Food & Function

Sprache

en

Online publication date

2018

Paginierung

6279 - 6286

Status

Published online

Herausgeber

Royal Society of Chemistry (RSC)

Herausgeber URL

http://dx.doi.org/10.1039/c8fo01804a

Datum der Datenerfassung

2024

Titel

Cytotoxicity of sesquiterpene alkaloids from <i>Nuphar</i> plants toward sensitive and drug-resistant cell lines

Ausgabe der Zeitschrift

9

Data source: Crossref

Abstract

Multi-drug resistance (MDR) is a critical problem in cancer chemotherapy. MDR causes the overexpression of ATP-binding cassette (ABC) transporters and mutations in tumor suppressor genes and oncogenes. To tackle this issue, in this study, we focused on Nuphar plants, which have been traditionally used as food. Sesquiterpene alkaloids (1-3) were isolated from N. japonicum and dimeric sesquiterpene thioalkaloids (4-10) were isolated from N. pumilum. P-glycoprotein-overexpressing CEM/ADR5000 cells were cross-resistant to 6,6'-dihydroxythiobinupharidine (10). Using in silico molecular docking, we calculated the binding energies and simulated the interactions of these compounds with the corresponding amino acid residues at the binding site of P-gp. In addition, we investigated the cytotoxicity of these compounds towards cell lines overexpressing other ABC transporters (BCRP, ABCB5), cell lines with a knocked out tumor suppressor gene TP53 or cell lines overexpressing a deletion-activated EGFR oncogene. These cell lines were sensitive or only minimally cross-resistant to these compounds compared with their corresponding wild-type cell lines.

Addresses

Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan. matsuda@mb.kyoto-phu.ac.jp.

Autoren

Masashi Fukaya
Seikou Nakamura
Mohamed Elamir F Hegazy
Yoshikazu Sugimoto
Noriko Hayashi
Souichi Nakashima
Masayuki Yoshikawa
Thomas Efferth
Hisashi Matsuda

DOI

10.1039/c8fo01804a

eISSN

2042-650X

Externe Identifier

PubMed Identifier: 30406781

Funding acknowledgements

Japan Society for the Promotion of Science: the Strategic Research Foundation at Private Universities
Alexander von Humboldt-Stiftung:
Ministry of Education, Culture, Sports, Science and Technology:
Houansha Foundation:
Japan Society for the Promotion of Science: JSPS KAKENHI Grant Number 17K08354

Open access

false

ISSN

2042-6496

Ausgabe der Veröffentlichung

12

Zeitschrift

Food & function

Schlüsselwörter

Cell Line, Tumor
Humans
Nuphar
Neoplasms
Sesquiterpenes
Alkaloids
Neoplasm Proteins
Plant Extracts
Antineoplastic Agents, Phytogenic
Cell Survival
Gene Expression Regulation, Neoplastic
Drug Resistance, Neoplasm
Molecular Docking Simulation
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1

Sprache

eng

Medium

Print

Paginierung

6279 - 6286

Datum der Veröffentlichung

2018

Status

Published

Datum der Datenerfassung

2018

Titel

Cytotoxicity of sesquiterpene alkaloids from Nuphar plants toward sensitive and drug-resistant cell lines.

Sub types

Journal Article

Ausgabe der Zeitschrift

9

Data source: Europe PubMed Central

Abstract

Multi-drug resistance (MDR) is a critical problem in cancer chemotherapy. MDR causes the overexpression of ATP-binding cassette (ABC) transporters and mutations in tumor suppressor genes and oncogenes. To tackle this issue, in this study, we focused on Nuphar plants, which have been traditionally used as food. Sesquiterpene alkaloids (1-3) were isolated from N. japonicum and dimeric sesquiterpene thioalkaloids (4-10) were isolated from N. pumilum. P-glycoprotein-overexpressing CEM/ADR5000 cells were cross-resistant to 6,6'-dihydroxythiobinupharidine (10). Using in silico molecular docking, we calculated the binding energies and simulated the interactions of these compounds with the corresponding amino acid residues at the binding site of P-gp. In addition, we investigated the cytotoxicity of these compounds towards cell lines overexpressing other ABC transporters (BCRP, ABCB5), cell lines with a knocked out tumor suppressor gene TP53 or cell lines overexpressing a deletion-activated EGFR oncogene. These cell lines were sensitive or only minimally cross-resistant to these compounds compared with their corresponding wild-type cell lines.

Autoren

Masashi Fukaya
Seikou Nakamura
Mohamed Elamir F Hegazy
Yoshikazu Sugimoto
Noriko Hayashi
Souichi Nakashima
Masayuki Yoshikawa
Thomas Efferth
Hisashi Matsuda

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/30406781

DOI

10.1039/c8fo01804a

eISSN

2042-650X

Ausgabe der Veröffentlichung

12

Zeitschrift

Food Funct

Schlüsselwörter

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
ATP Binding Cassette Transporter, Subfamily G, Member 2
Alkaloids
Antineoplastic Agents, Phytogenic
Cell Line, Tumor
Cell Survival
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Humans
Molecular Docking Simulation
Neoplasm Proteins
Neoplasms
Nuphar
Plant Extracts
Sesquiterpenes

Sprache

eng

Country

England

Paginierung

6279 - 6286

Datum der Veröffentlichung

2018

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2019

Titel

Cytotoxicity of sesquiterpene alkaloids from Nuphar plants toward sensitive and drug-resistant cell lines.

Sub types

Journal Article

Ausgabe der Zeitschrift

9

Data source: PubMed

Cytotoxicity of sesquiterpene alkaloids from Nuphar plants toward sensitive and drug-resistant cell lines

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