Xanthohumol suppresses oestrogen-signalling in breast cancer through the inhibition of BIG3-PHB2 interactions

Tetsuro Yoshimaru, Masato Komatsu, Etsu Tashiro, Masaya Imoto, Hiroyuki Osada, Yasuo Miyoshi, Junko Honda, Mitsunori Sasa, Toyomasa Katagiri

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Xanthohumol (XN) is a natural anticancer compound that inhibits the proliferation of oestrogen receptor-α (ERα)-positive breast cancer cells. However, the precise mechanism of the antitumour effects of XN on oestrogen (E2)-dependent cell growth, and especially its direct target molecule(s), remain(s) largely unknown. Here, we focus on whether XN directly binds to the tumour suppressor protein prohibitin 2 (PHB2), forming a novel natural antitumour compound targeting the BIG3-PHB2 complex and acting as a pivotal modulator of E2/ERα signalling in breast cancer cells. XN treatment effectively prevented the BIG3-PHB2 interaction, thereby releasing PHB2 to directly bind to both nuclear- and cytoplasmic ERα. This event led to the complete suppression of the E2-signalling pathways and ERα-positive breast cancer cell growth both in vitro and in vivo, but did not suppress the growth of normal mammary epithelial cells. Our findings suggest that XN may be a promising natural compound to suppress the growth of luminal-type breast cancer.

Original languageEnglish
Article number7355
JournalScientific Reports
Volume4
DOIs
Publication statusPublished - 2014 Dec 8

Fingerprint

Estrogens
Breast Neoplasms
Growth
Tumor Suppressor Proteins
Estrogen Receptors
Breast
Epithelial Cells
xanthohumol
prohibitin

ASJC Scopus subject areas

  • General

Cite this

Xanthohumol suppresses oestrogen-signalling in breast cancer through the inhibition of BIG3-PHB2 interactions. / Yoshimaru, Tetsuro; Komatsu, Masato; Tashiro, Etsu; Imoto, Masaya; Osada, Hiroyuki; Miyoshi, Yasuo; Honda, Junko; Sasa, Mitsunori; Katagiri, Toyomasa.

In: Scientific Reports, Vol. 4, 7355, 08.12.2014.

Research output: Contribution to journalArticle

Yoshimaru, Tetsuro ; Komatsu, Masato ; Tashiro, Etsu ; Imoto, Masaya ; Osada, Hiroyuki ; Miyoshi, Yasuo ; Honda, Junko ; Sasa, Mitsunori ; Katagiri, Toyomasa. / Xanthohumol suppresses oestrogen-signalling in breast cancer through the inhibition of BIG3-PHB2 interactions. In: Scientific Reports. 2014 ; Vol. 4.
@article{cd955b2fef6c4a40a2b5d3a023c33354,
title = "Xanthohumol suppresses oestrogen-signalling in breast cancer through the inhibition of BIG3-PHB2 interactions",
abstract = "Xanthohumol (XN) is a natural anticancer compound that inhibits the proliferation of oestrogen receptor-α (ERα)-positive breast cancer cells. However, the precise mechanism of the antitumour effects of XN on oestrogen (E2)-dependent cell growth, and especially its direct target molecule(s), remain(s) largely unknown. Here, we focus on whether XN directly binds to the tumour suppressor protein prohibitin 2 (PHB2), forming a novel natural antitumour compound targeting the BIG3-PHB2 complex and acting as a pivotal modulator of E2/ERα signalling in breast cancer cells. XN treatment effectively prevented the BIG3-PHB2 interaction, thereby releasing PHB2 to directly bind to both nuclear- and cytoplasmic ERα. This event led to the complete suppression of the E2-signalling pathways and ERα-positive breast cancer cell growth both in vitro and in vivo, but did not suppress the growth of normal mammary epithelial cells. Our findings suggest that XN may be a promising natural compound to suppress the growth of luminal-type breast cancer.",
author = "Tetsuro Yoshimaru and Masato Komatsu and Etsu Tashiro and Masaya Imoto and Hiroyuki Osada and Yasuo Miyoshi and Junko Honda and Mitsunori Sasa and Toyomasa Katagiri",
year = "2014",
month = "12",
day = "8",
doi = "10.1038/srep07355",
language = "English",
volume = "4",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Xanthohumol suppresses oestrogen-signalling in breast cancer through the inhibition of BIG3-PHB2 interactions

AU - Yoshimaru, Tetsuro

AU - Komatsu, Masato

AU - Tashiro, Etsu

AU - Imoto, Masaya

AU - Osada, Hiroyuki

AU - Miyoshi, Yasuo

AU - Honda, Junko

AU - Sasa, Mitsunori

AU - Katagiri, Toyomasa

PY - 2014/12/8

Y1 - 2014/12/8

N2 - Xanthohumol (XN) is a natural anticancer compound that inhibits the proliferation of oestrogen receptor-α (ERα)-positive breast cancer cells. However, the precise mechanism of the antitumour effects of XN on oestrogen (E2)-dependent cell growth, and especially its direct target molecule(s), remain(s) largely unknown. Here, we focus on whether XN directly binds to the tumour suppressor protein prohibitin 2 (PHB2), forming a novel natural antitumour compound targeting the BIG3-PHB2 complex and acting as a pivotal modulator of E2/ERα signalling in breast cancer cells. XN treatment effectively prevented the BIG3-PHB2 interaction, thereby releasing PHB2 to directly bind to both nuclear- and cytoplasmic ERα. This event led to the complete suppression of the E2-signalling pathways and ERα-positive breast cancer cell growth both in vitro and in vivo, but did not suppress the growth of normal mammary epithelial cells. Our findings suggest that XN may be a promising natural compound to suppress the growth of luminal-type breast cancer.

AB - Xanthohumol (XN) is a natural anticancer compound that inhibits the proliferation of oestrogen receptor-α (ERα)-positive breast cancer cells. However, the precise mechanism of the antitumour effects of XN on oestrogen (E2)-dependent cell growth, and especially its direct target molecule(s), remain(s) largely unknown. Here, we focus on whether XN directly binds to the tumour suppressor protein prohibitin 2 (PHB2), forming a novel natural antitumour compound targeting the BIG3-PHB2 complex and acting as a pivotal modulator of E2/ERα signalling in breast cancer cells. XN treatment effectively prevented the BIG3-PHB2 interaction, thereby releasing PHB2 to directly bind to both nuclear- and cytoplasmic ERα. This event led to the complete suppression of the E2-signalling pathways and ERα-positive breast cancer cell growth both in vitro and in vivo, but did not suppress the growth of normal mammary epithelial cells. Our findings suggest that XN may be a promising natural compound to suppress the growth of luminal-type breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=84923250141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923250141&partnerID=8YFLogxK

U2 - 10.1038/srep07355

DO - 10.1038/srep07355

M3 - Article

VL - 4

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 7355

ER -