PMID- 32701561
OWN - NLM
STAT- MEDLINE
DCOM- 20210831
LR  - 20211204
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 31
IP  - 10
DP  - 2020 Nov
TI  - Icaritin inhibits lung cancer-induced osteoclastogenesis by suppressing the 
      expression of IL-6 and TNF-a and through AMPK/mTOR signaling pathway.
PG  - 1004-1011
LID - 10.1097/CAD.0000000000000976 [doi]
AB  - Bone metastasis is one of the common phenomena in the late stage of lung cancer. 
      Inhibition of bone metastasis can improve the survival of lung cancer patients. 
      However, the current drugs for the treatment of bone metastasis have shown little 
      effect on overall survival. Therefore, there is an urgent necessity to identify 
      novel drugs capable of preventing and treating bone metastasis of lung cancer. 
      Our study determined that icaritin (ICT) can inhibit lung cancer-mediated 
      osteoclastogenesis and induce the apoptosis of osteoclasts. Exposure to ICT 
      increased the activation of adenosine 5'-monophosphate-activated protein kinase 
      (AMPK), reduced the activation of mammalian target of rapamycin (mTOR) and 
      decreased the expression of bcl-2. The bioactivity of ICT on osteoclastogenesis 
      was associated with the regulation of the AMPK/mTOR signaling pathway. Blocking 
      AMPK significantly increased osteoclast differentiation, decreased osteoclast 
      apoptosis and canceled the effects of ICT on the phosphorylation of AMPK as well 
      as the inhibition of mTOR and bcl-2. Furthermore, ICT decreased the levels of 
      IL-6 and TNF-alpha in osteoclasts, while the AMPK inhibitor compound C significantly 
      abolished the inhibitory effects of ICT on IL-6 and TNF-alpha. Thus, the present 
      study demonstrated that ICT may be a potential natural agent for the treatment of 
      bone metastasis in patients with lung cancer.
FAU - Zhao, Xueqiang
AU  - Zhao X
AD  - Department of Respiratory Medicine, The Second Affiliated Hospital of Guilin 
      Medical University.
FAU - Lin, Yun
AU  - Lin Y
AD  - Department of Respiratory Medicine, The Second Affiliated Hospital of Guilin 
      Medical University.
FAU - Jiang, Bijia
AU  - Jiang B
AD  - Department of Respiratory Medicine, The Second Affiliated Hospital of Guilin 
      Medical University.
FAU - Yin, Jianhua
AU  - Yin J
AD  - Department of Respiratory Medicine, The Second Affiliated Hospital of Guilin 
      Medical University.
FAU - Lu, Chunlan
AU  - Lu C
AD  - Department of Respiratory Medicine, The Second Affiliated Hospital of Guilin 
      Medical University.
FAU - Wang, Juan
AU  - Wang J
AD  - College of Pharmacy, Guilin Medical University.
AD  - Research Center for Science, Guilin Medical University, Guilin, Guangxi Zhuang, 
      P.R. China.
FAU - Zeng, Jinrong
AU  - Zeng J
AD  - Department of Respiratory Medicine, The Second Affiliated Hospital of Guilin 
      Medical University.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Flavonoids)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (interleukin-6, mouse)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - UFE666UELY (icaritin)
SB  - IM
MH  - A549 Cells
MH  - AMP-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Flavonoids/*pharmacology
MH  - Humans
MH  - Interleukin-6/metabolism
MH  - Lung Neoplasms/*drug therapy/metabolism/*pathology
MH  - Mice
MH  - Osteoclasts/drug effects/pathology
MH  - Osteogenesis/*drug effects/physiology
MH  - RAW 264.7 Cells
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2020/07/24 06:00
MHDA- 2021/09/01 06:00
CRDT- 2020/07/24 06:00
PHST- 2020/07/24 06:00 [pubmed]
PHST- 2021/09/01 06:00 [medline]
PHST- 2020/07/24 06:00 [entrez]
AID - 00001813-202011000-00003 [pii]
AID - 10.1097/CAD.0000000000000976 [doi]
PST - ppublish
SO  - Anticancer Drugs. 2020 Nov;31(10):1004-1011. doi: 10.1097/CAD.0000000000000976.