PMID- 35676792
OWN - NLM
STAT- MEDLINE
DCOM- 20220610
LR  - 20220610
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 151
DP  - 2022 Jul
TI  - Cytotoxic effect of metformin on butyrate-resistant PMF-K014 colorectal cancer 
      spheroid cells.
PG  - 113214
LID - S0753-3322(22)00603-5 [pii]
LID - 10.1016/j.biopha.2022.113214 [doi]
AB  - Three-dimensional (3D) cell culture models are used in cancer research because 
      they mimic physiological responses in vivo compared with two-dimensional (2D) 
      culture systems. Recently, cross-resistance of butyrate-resistant (BR) cells and 
      chemoresistance in colorectal cancer (CRC) cells have been reported; however, 
      effective treatments for BR cells have not been identified. In this study, we 
      investigated the cytotoxicity of metformin (MET), an anti-diabetic drug, on BR 
      CRC cells in a 3D spheroid culture model. The results demonstrate that MET 
      decreases spheroid size, migration, and spheroid viability, while it increases 
      spheroid death. The molecular mechanism revealed that AMP-activated protein 
      kinase (AMPK) and Akt serine/threonine kinase 1(Akt) were significantly 
      upregulated, whereas the acetyl-CoA-carboxylase (ACC) and mammalian target of 
      rapamycin (mTOR) were downregulated, which led to caspase activation and 
      apoptosis. Our findings show the potential cytotoxicity of MET on CRC-BR cells. 
      The combination of MET and conventional chemotherapeutic drugs should be 
      addressed in further studies to reduce the side effects of standard chemotherapy 
      for CRC.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Nittayaboon, Kesara
AU  - Nittayaboon K
AD  - Department of Biomedical Sciences and Biomedical Engineering, Faculty of 
      Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand. 
      Electronic address: kesara.nittayaboon@gmail.com.
FAU - Leetanaporn, Kittinun
AU  - Leetanaporn K
AD  - Department of Biomedical Sciences and Biomedical Engineering, Faculty of 
      Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand. 
      Electronic address: lkittinun1@gmail.com.
FAU - Sangkhathat, Surasak
AU  - Sangkhathat S
AD  - Department of Biomedical Sciences and Biomedical Engineering, Faculty of 
      Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand. 
      Electronic address: s.sangkhathat@gmail.com.
FAU - Roytrakul, Sittirak
AU  - Roytrakul S
AD  - National Center for Genetic Engineering and Biotechnology (BIOTEC), National 
      Science and Technology Development Agency, Pathumthani 12120, Thailand. 
      Electronic address: sittiruk@biotec.or.th.
FAU - Navakanitworakul, Raphatphorn
AU  - Navakanitworakul R
AD  - Department of Biomedical Sciences and Biomedical Engineering, Faculty of 
      Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand. 
      Electronic address: nraphatp@medicine.psu.ac.th.
LA  - eng
PT  - Journal Article
DEP - 20220528
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Butyrates)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - *Antineoplastic Agents/pharmacology/therapeutic use
MH  - Butyrates/pharmacology/therapeutic use
MH  - Cell Line, Tumor
MH  - *Colorectal Neoplasms/drug therapy
MH  - Humans
MH  - *Metformin/pharmacology/therapeutic use
MH  - Proto-Oncogene Proteins c-akt/metabolism
OTO - NOTNLM
OT  - Butyrate resistance
OT  - Colorectal cancer cell
OT  - Metformin
OT  - Spheroid cell
EDAT- 2022/06/10 06:00
MHDA- 2022/06/11 06:00
CRDT- 2022/06/09 01:07
PHST- 2022/02/27 00:00 [received]
PHST- 2022/05/24 00:00 [revised]
PHST- 2022/05/26 00:00 [accepted]
PHST- 2022/06/09 01:07 [entrez]
PHST- 2022/06/10 06:00 [pubmed]
PHST- 2022/06/11 06:00 [medline]
AID - S0753-3322(22)00603-5 [pii]
AID - 10.1016/j.biopha.2022.113214 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2022 Jul;151:113214. doi: 10.1016/j.biopha.2022.113214. Epub 
      2022 May 28.