PMID- 28668827
OWN - NLM
STAT- MEDLINE
DCOM- 20170829
LR  - 20211204
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 37
IP  - 7
DP  - 2017 Jul
TI  - A Novel mTOR Inhibitor; Anthracimycin for the Treatment of Human Hepatocellular 
      Carcinoma.
PG  - 3397-3403
AB  - BACKGROUND/AIM: Anthracimycin, a secondary metabolite of Streptomyces, has been 
      shown to inhibit the invasion of certain cancer cell lines. MATERIALS AND 
      METHODS: In this study we evaluated the effect of anthracimycin on cell growth 
      and signaling pathways in hepatocellular carcinoma (HCC). RESULTS: Anthracimycin 
      suppressed cell proliferation and motility and induced apoptosis in human HCC 
      cell lines. Furthermore, anthracimycin had no effect on the enrichment of 
      EpCAM-high liver cancer stem cells (CSCs), while fluorouracil dramatically 
      enriched the CSCs with activation of the stemness-related genes EPCAM and SOX9 in 
      HuH7 cells. Mechanistically, anthracimycin suppressed mammalian target of 
      rapamycin (mTOR) signaling, and was most effective at inhibiting HCC cell 
      proliferation with mTOR activation. CONCLUSION: Anthracimycin is a novel mTOR 
      inhibitor capable of suppressing the proliferation of CSCs and non-CSCs equally 
      well in HCC, and it is suggested that anthracimycin could be effective in the 
      eradication of HCC associated with mTOR-signaling activation.
CI  - Copyright(c) 2017, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Hayashi, Tomoyuki
AU  - Hayashi T
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Yamashita, Taro
AU  - Yamashita T
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan taroy@m-kanazawa.jp.
AD  - Department of General Medicine, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Okada, Hikari
AU  - Okada H
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Oishi, Naoki
AU  - Oishi N
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Sunagozaka, Hajime
AU  - Sunagozaka H
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Nio, Kouki
AU  - Nio K
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Hayashi, Takehiro
AU  - Hayashi T
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Hara, Yasumasa
AU  - Hara Y
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Asahina, Yoshiro
AU  - Asahina Y
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Yoshida, Mariko
AU  - Yoshida M
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Hashiba, Tomomi
AU  - Hashiba T
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Suda, Tsuyoshi
AU  - Suda T
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Shirasaki, Takayoshi
AU  - Shirasaki T
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Igarashi, Yasuhiro
AU  - Igarashi Y
AD  - Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural 
      University, Imizu, Japan.
FAU - Miyanouchi, Koji
AU  - Miyanouchi K
AD  - Bio Technical Research Industry Co. Ltd., Kanazawa, Japan.
FAU - Yamashita, Tatsuya
AU  - Yamashita T
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Honda, Masao
AU  - Honda M
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
FAU - Kaneko, Shuichi
AU  - Kaneko S
AD  - Department of Gastroenterology, Kanazawa University Graduate School of Medical 
      Science, Kanazawa, Japan.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Epithelial Cell Adhesion Molecule)
RN  - 0 (Polyketides)
RN  - 0 (anthracimycin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Carcinoma, Hepatocellular/*drug therapy/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Epithelial Cell Adhesion Molecule/metabolism
MH  - Fluorouracil/pharmacology
MH  - Humans
MH  - Liver Neoplasms/*drug therapy/metabolism
MH  - Neoplastic Stem Cells/drug effects/metabolism
MH  - Polyketides/*pharmacology
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
OTO - NOTNLM
OT  - Anthracimycin
OT  - cancer stem cells
OT  - hepatocellular carcinoma
OT  - mammalian target of rapamycin
EDAT- 2017/07/03 06:00
MHDA- 2017/08/30 06:00
CRDT- 2017/07/03 06:00
PHST- 2017/04/27 00:00 [received]
PHST- 2017/05/24 00:00 [revised]
PHST- 2017/05/25 00:00 [accepted]
PHST- 2017/07/03 06:00 [entrez]
PHST- 2017/07/03 06:00 [pubmed]
PHST- 2017/08/30 06:00 [medline]
AID - 37/7/3397 [pii]
AID - 10.21873/anticanres.11706 [doi]
PST - ppublish
SO  - Anticancer Res. 2017 Jul;37(7):3397-3403. doi: 10.21873/anticanres.11706.