TY - JOUR
T1 - Endocrine therapy-resistant breast cancer model cells are inhibited by soybean glyceollin I through Eleanor non-coding RNA
AU - Yamamoto, Tatsuro
AU - Sakamoto, Chiyomi
AU - Tachiwana, Hiroaki
AU - Kumabe, Mitsuru
AU - Matsui, Toshiro
AU - Yamashita, Tadatoshi
AU - Shinagawa, Masatoshi
AU - Ochiai, Koji
AU - Saitoh, Noriko
AU - Nakao, Mitsuyoshi
N1 - Funding Information:
We thank all members of the Nakao and Saitoh laboratories for their support. We appreciate technical assistants by Drs. Yuka Sakata (The Cancer Institute of JFCR) and Tomoaki Koga (Kumamoto University). We also thank Dr. Hideki Nakayama (Kumamoto University) for his support. This work was supported by the JSPS KAKENHI (16H04744, 18H05531 and 18K19310 [to N.S.], 15H04707 and 18K19479 [to M.N.]), research grants from The Astellas Foundation for Research on Metabolic Disorders and The Uehara Memorial Foundation (to N.S.), The Mitsubishi Foundation (to M.N.), and the Strategic Core Technology Advancement Program (Supporting Industry Program) from the Ministry of Economy, Trade and Industry (K.O., T.M., M.N. and N.S.).
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Long-term estrogen deprivation (LTED) of an estrogen receptor (ER) α-positive breast cancer cell line recapitulates cancer cells that have acquired estrogen-independent cell proliferation and endocrine therapy resistance. Previously, we have shown that a cluster of non-coding RNAs, Eleanors (ESR1 locus enhancing and activating non-coding RNAs) formed RNA cloud and upregulated the ESR1 gene in the nuclei of LTED cells. Eleanors were inhibited by resveratrol through ER. Here we prepared another polyphenol, glyceollin I from stressed soybeans, and identified it as a major inhibitor of the Eleanor RNA cloud and ESR1 mRNA transcription. The inhibition was independent of ER, unlike one by resveratrol. This was consistent with a distinct tertiary structure of glyceollin I for ER binding. Glyceollin I preferentially inhibited the growth of LTED cells and induced apoptosis. Our results suggest that glyceollin I has a novel role in LTED cell inhibition through Eleanors. In other words, LTED cells or endocrine therapy-resistant breast cancer cells may be ready for apoptosis, which can be triggered with polyphenols both in ER-dependent and ER-independent manners.
AB - Long-term estrogen deprivation (LTED) of an estrogen receptor (ER) α-positive breast cancer cell line recapitulates cancer cells that have acquired estrogen-independent cell proliferation and endocrine therapy resistance. Previously, we have shown that a cluster of non-coding RNAs, Eleanors (ESR1 locus enhancing and activating non-coding RNAs) formed RNA cloud and upregulated the ESR1 gene in the nuclei of LTED cells. Eleanors were inhibited by resveratrol through ER. Here we prepared another polyphenol, glyceollin I from stressed soybeans, and identified it as a major inhibitor of the Eleanor RNA cloud and ESR1 mRNA transcription. The inhibition was independent of ER, unlike one by resveratrol. This was consistent with a distinct tertiary structure of glyceollin I for ER binding. Glyceollin I preferentially inhibited the growth of LTED cells and induced apoptosis. Our results suggest that glyceollin I has a novel role in LTED cell inhibition through Eleanors. In other words, LTED cells or endocrine therapy-resistant breast cancer cells may be ready for apoptosis, which can be triggered with polyphenols both in ER-dependent and ER-independent manners.
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U2 - 10.1038/s41598-018-33227-y
DO - 10.1038/s41598-018-33227-y
M3 - Article
C2 - 30315184
AN - SCOPUS:85054890747
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 15202
ER -
