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

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

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6279-6286
Number of pages8
JournalFood and Function
Volume9
Issue number12
DOIs
Publication statusPublished - 2018

ASJC Scopus subject areas

  • Food Science

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