TY - JOUR
T1 - Methyl-β-cyclodextrin potentiates the BITC-induced anti-cancer effect through modulation of the Akt phosphorylation in human colorectal cancer cells
AU - Yang, Qifu
AU - Miyagawa, Miku
AU - Liu, Xiaoyang
AU - Zhu, Beiwei
AU - Munemasa, Shintaro
AU - Nakamura, Toshiyuki
AU - Murata, Yoshiyuki
AU - Nakamura, Yoshimasa
N1 - Funding Information:
This study was partly supported by MEXT KAKENHI Grant Number 25292073, 16K14928, and 17H03818 (YN).
Publisher Copyright:
© 2018 Japan Society for Bioscience, Biotechnology, and Agrochemistry.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Akt
KW - Apoptosis
KW - Benzyl isothiocyanate
KW - Cholesterol
KW - Methyl-β-cyclodextrin
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U2 - 10.1080/09168451.2018.1514249
DO - 10.1080/09168451.2018.1514249
M3 - Article
C2 - 30200817
AN - SCOPUS:85056300506
SN - 0916-8451
VL - 82
SP - 2158
EP - 2167
JO - Bioscience, Biotechnology and Biochemistry
JF - Bioscience, Biotechnology and Biochemistry
IS - 12
ER -
