PMID- 33461474
OWN - NLM
STAT- MEDLINE
DCOM- 20220428
LR  - 20220428
IS  - 1875-5992 (Electronic)
IS  - 1871-5206 (Linking)
VI  - 22
IP  - 4
DP  - 2022
TI  - Antineoplastic Activity of an Old Natural Antidiabetic Biguanide on the Human 
      Thyroid Carcinoma Cell Line.
PG  - 713-720
LID - 10.2174/1871520621666210118093532 [doi]
AB  - BACKGROUND: In the last decades, metformin (Met), an herbal anti-diabetic 
      medicine, has been proposed as an anti-cancer agent. OBJECTIVE: Thyroid cancers 
      are the most common malignancy of the endocrine system. Therefore, the current 
      study was performed to assess the effects of Met on cell proliferation and 
      activation of the Phosphoinositide 3- Kinase (PI3K)/Protein kinase B 
      (AKT)/Forkhead Box O1 (FOXO1) signaling pathway in the Medullary Thyroid 
      Carcinoma (MTC) cells. The effects of Met on the expression of REarranged during 
      Transfection (RET) proto-oncogene were also investigated. METHODS: MTC cell line 
      (TT) was treated with 0, 2.5, 5, 10, 20, 30, 40, 50, and 60 mM concentrations of 
      Met for 24, 48, and 72h. The viability and apoptosis of the treated cells were 
      measured by the 3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide 
      (MTT) and Annexin V- Propidium Iodide (PI) assays. The expression level of PI3K, 
      AKT, FOXO1, and RET genes was investigated by quantitative Real-Time Polymerase 
      Chain Reaction (qRT-PCR), and phosphorylation of their proteins was determined by 
      the Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Results showed that Met 
      significantly decreased the viability of the MTC cells. Met also reduced the 
      expression level of PI3K, AKT, and FOXO1 genes (P<0.05), whereas it elevated the 
      expression level of RET proto-oncogene (P<0.05). CONCLUSION: It seems that the 
      Met has a cytostatic effect on the TT cells. Our results showed that anti-tumoral 
      effects of Met may be cell type-specific, and according to the induction of RET 
      (as a proto-oncogene) and inhibition of FOXO1 (as a tumor suppressor gene), Met 
      could not be an appropriate agent in the treatment of MTC. The antineoplastic 
      activity of Met has been confirmed against several malignancies in "in vitro" and 
      "in vivo" studies. However, its molecular mechanisms in the treatment of 
      different carcinomas particularly in thyroid cancers are not clearly understood 
      and more studies are required to confirm its exact effect on the MTC.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Nozhat, Zahra
AU  - Nozhat Z
AD  - Cellular and Molecular Endocrine Research Center, Research Institute of Endocrine 
      Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
FAU - Zarkesh, Maryam
AU  - Zarkesh M
AD  - Cellular and Molecular Endocrine Research Center, Research Institute of Endocrine 
      Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
FAU - Baldini, Enke
AU  - Baldini E
AD  - Department of Surgical Sciences, University of Rome, Rome, Italy.
FAU - Mohammadi-Yeganeh, Samira
AU  - Mohammadi-Yeganeh S
AD  - Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid 
      Beheshti University of Medical Sciences, Tehran, Iran.
FAU - Azizi, Feridoun
AU  - Azizi F
AD  - Endocrine Research Center, Research Institute for Endocrine Sciences, School of 
      Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
FAU - Hedayati, Mehdi
AU  - Hedayati M
AD  - Cellular and Molecular Endocrine Research Center, Research Institute of Endocrine 
      Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Anticancer Agents Med Chem
JT  - Anti-cancer agents in medicinal chemistry
JID - 101265649
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biguanides)
RN  - 0 (Hypoglycemic Agents)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - Thyroid cancer, medullary
SB  - IM
MH  - *Antineoplastic Agents/pharmacology/therapeutic use
MH  - Biguanides/pharmacology
MH  - *Carcinoma, Neuroendocrine/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology/therapeutic use
MH  - Phosphatidylinositol 3-Kinases
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Proto-Oncogene Proteins c-ret/genetics/metabolism
MH  - *Thyroid Neoplasms/drug therapy
OTO - NOTNLM
OT  - Thyroid cancer
OT  - biguanides
OT  - cell signalling
OT  - diabetes
OT  - metformin
OT  - proliferation
EDAT- 2021/01/20 06:00
MHDA- 2022/04/29 06:00
CRDT- 2021/01/19 05:37
PHST- 2020/07/16 00:00 [received]
PHST- 2020/11/06 00:00 [revised]
PHST- 2020/11/17 00:00 [accepted]
PHST- 2021/01/20 06:00 [pubmed]
PHST- 2022/04/29 06:00 [medline]
PHST- 2021/01/19 05:37 [entrez]
AID - ACAMC-EPUB-113352 [pii]
AID - 10.2174/1871520621666210118093532 [doi]
PST - ppublish
SO  - Anticancer Agents Med Chem. 2022;22(4):713-720. doi: 
      10.2174/1871520621666210118093532.