PMID- 34545650
OWN - NLM
STAT- MEDLINE
DCOM- 20211125
LR  - 20211204
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 35
IP  - 11
DP  - 2021 Nov
TI  - Harmaline isolated from Peganum harmala suppresses growth of esophageal squamous 
      cell carcinoma through targeting mTOR.
PG  - 6377-6388
LID - 10.1002/ptr.7289 [doi]
AB  - Harmaline is a naturally occurring beta-carboline alkaloid that is isolated from 
      Peganum harmala. It has shown efficacy in treating Parkinson's disease and has 
      been reported to exhibit antimicrobial and anticancer properties. However, the 
      molecular mechanism of harmaline in the context of esophageal squamous cell 
      carcinoma (ESCC) has not been characterized. Here, we report that harmaline 
      attenuates ESCC growth by directly targeting the mammalian target of rapamycin 
      (mTOR). Harmaline strongly reduced cell proliferation and anchorage-independent 
      cell growth. Additionally, harmaline treatment induced G2/M phase cell-cycle 
      arrest through upregulation of p27. The results of in vitro and cell-based assays 
      showed that harmaline directly inhibited the activity of mTOR kinase and the 
      phosphorylation of its downstream pathway components. Depletion of mTOR using an 
      shRNA-mediated strategy in ESCC cell lines indicated that reduced mTOR protein 
      expression levels are correlated with decreased cell proliferation. Additionally, 
      we observed that the inhibitory effect of harmaline was dependent upon mTOR 
      expression. Notably, oral administration of harmaline suppressed ESCC 
      patient-derived tumor growth in vivo. Taken together, harmaline is a potential 
      mTOR inhibitor that might be used for therapeutically treating ESCC.
CI  - (c) 2021 John Wiley & Sons Ltd.
FAU - Zhang, Yuanyuan
AU  - Zhang Y
AD  - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou, China.
AD  - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
FAU - Shi, Xiaodan
AU  - Shi X
AD  - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
FAU - Xie, Xiaomeng
AU  - Xie X
AD  - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou, China.
AD  - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
FAU - Laster, Kyle Vaughn
AU  - Laster KV
AD  - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
FAU - Pang, Mengjun
AU  - Pang M
AD  - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou, China.
AD  - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
FAU - Liu, Kangdong
AU  - Liu K
AD  - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou, China.
AD  - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
AD  - The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China.
AD  - The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, 
      Zhengzhou, China.
AD  - International Joint Research Center of Cancer Chemoprevention, Zhengzhou, China.
FAU - Hwang, Joonsung
AU  - Hwang J
AD  - Korea Research Institute of Bioscience and Biotechnology (KRIBB), Anticancer 
      Agent Research Center, Cheongju, Republic of Korea.
FAU - Kim, Dong Joon
AU  - Kim DJ
AUID- ORCID: 0000-0001-6910-9213
AD  - The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou 
      University, Zhengzhou, China.
AD  - China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
AD  - The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, 
      Zhengzhou, China.
LA  - eng
GR  - 81872335/General project, National Natural Science Foundation China/
GR  - 82103193/General project, National Natural Science Foundation China (NSFC)/
GR  - U1804196/Henan Joint Fund, China/
GR  - 212300410315/Youth Science Foundation of Natural Science Foundation of Henan 
      Province, China/
PT  - Journal Article
DEP - 20210920
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - CN58I4TOET (Harmaline)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - *Esophageal Neoplasms/drug therapy
MH  - *Esophageal Squamous Cell Carcinoma/drug therapy
MH  - Harmaline/pharmacology
MH  - *Head and Neck Neoplasms
MH  - Humans
MH  - *Peganum
MH  - Sirolimus
MH  - TOR Serine-Threonine Kinases
OTO - NOTNLM
OT  - Harmaline
OT  - cell proliferation
OT  - esophageal squamous cell carcinoma
OT  - mTOR
OT  - patient-derived xenograft
EDAT- 2021/09/22 06:00
MHDA- 2021/11/26 06:00
CRDT- 2021/09/21 06:48
PHST- 2021/08/19 00:00 [revised]
PHST- 2021/04/05 00:00 [received]
PHST- 2021/09/03 00:00 [accepted]
PHST- 2021/09/22 06:00 [pubmed]
PHST- 2021/11/26 06:00 [medline]
PHST- 2021/09/21 06:48 [entrez]
AID - 10.1002/ptr.7289 [doi]
PST - ppublish
SO  - Phytother Res. 2021 Nov;35(11):6377-6388. doi: 10.1002/ptr.7289. Epub 2021 Sep 
      20.