Methyl-β-cyclodextrin potentiates the BITC-induced anti-cancer effect through modulation of the Akt phosphorylation in human colorectal cancer cells

Qifu Yang, Miku Miyagawa, Xiaoyang Liu, Beiwei Zhu, Shintaro Munemasa, Toshiyuki Nakamura, Yoshiyuki Murata, Yoshimasa Nakamura

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Methyl-β-cyclodextrin (MβCD) is an effective agent for the removal of plasma membrane cholesterol. In this study, we investigated the modulating effects of MβCD on the antiproliferation induced by benzyl isothiocyanate (BITC), an ITC compound mainly derived from papaya seeds. We confirmed that MβCD dose-dependently increased the cholesterol level in the medium, possibly through its removal from the plasma membrane of human colorectal cancer cells. The pretreatment with a non-toxic concentration (2.5 mM) of MβCD significantly enhanced the BITC-induced cytotoxicity and apoptosis induction, which was counteracted by the cholesterol supplementation. Although BITC activated the phosphoinositide 3-kinase (PI3K)/Akt pathway, MβCD dose-dependently inhibited the phosphorylation level of Akt. On the contrary, the treatment of MβCD enhanced the phosphorylation of mitogen activated protein kinases, but did not potentiate their BITC-induced phosphorylation. These results suggested that MβCD might potentiate the BITC-induced anti-cancer by cholesterol depletion and thus inhibition of the PI3K/Akt-dependent survival pathway.

Original languageEnglish
Pages (from-to)2158-2167
Number of pages10
JournalBioscience, Biotechnology and Biochemistry
Volume82
Issue number12
DOIs
Publication statusPublished - Jan 1 2018

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Keywords

  • Akt
  • Apoptosis
  • Benzyl isothiocyanate
  • Cholesterol
  • Methyl-β-cyclodextrin

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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