PMID- 33125108
OWN - NLM
STAT- MEDLINE
DCOM- 20210802
LR  - 20231213
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 44
IP  - 6
DP  - 2020 Dec
TI  - Effects and mechanisms of fatty acid metabolism‑mediated glycolysis regulated by 
      betulinic acid‑loaded nanoliposomes in colorectal cancer.
PG  - 2595-2609
LID - 10.3892/or.2020.7787 [doi]
AB  - Although previous studies have demonstrated that triterpenoids, such as betulinic 
      acid (BA), can inhibit tumor cell growth, their potential targets in colorectal 
      cancer (CRC) metabolism have not been systematically investigated. In the present 
      study, BA‑loaded nanoliposomes (BA‑NLs) were prepared, and their effects on CRC 
      cell lines were evaluated. The aim of the present study was to determine the 
      anticancer mechanisms of action of BA‑NLs in fatty acid metabolism‑mediated 
      glycolysis, and investigate the role of key targets, such as acyl‑CoA synthetase 
      (ACSL), carnitine palmitoyltransferase (CPT) and acetyl CoA, in promoting 
      glycolysis, which is activated by inducing hexokinase (HK), phosphofructokinase‑1 
      (PFK‑1), phosphoenolpyruvate (PEP) and pyruvate kinase (PK) expression. The 
      results demonstrated that BA‑NLs significantly suppressed the proliferation and 
      glucose uptake of CRC cells by regulating potential glycolysis and fatty acid 
      metabolism targets and pathways, which forms the basis of the anti‑CRC function 
      of BA‑NLs. Moreover, the effects of BA‑NLs were further validated by 
      demonstrating that the key targets of HK2, PFK‑1, PEP and PK isoenzyme M2 (PKM2) 
      in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked 
      by BA‑NLs, which play key roles in the inhibition of glycolysis and fatty 
      acid‑mediated production of pyruvate and lactate. The results of the present 
      study may provide a deeper understanding supporting the hypothesis that liposomal 
      BA may regulate alternative metabolic pathways implicated in CRC adjuvant 
      therapy.
FAU - Wang, Gang
AU  - Wang G
AD  - Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu 
      University, Shanghai 200235, P.R. China.
FAU - Yu, Yang
AU  - Yu Y
AD  - Jiangsu University School of Pharmacy, Zhenjiang, Jiangsu 212001, P.R. China.
FAU - Wang, Yu-Zhu
AU  - Wang YZ
AD  - Jiangsu University School of Pharmacy, Zhenjiang, Jiangsu 212001, P.R. China.
FAU - Zhu, Zhi-Min
AU  - Zhu ZM
AD  - Department of Pharmaceutics, Shanghai Eighth People's Hospital, Jiangsu 
      University, Shanghai 200235, P.R. China.
FAU - Yin, Pei-Hao
AU  - Yin PH
AD  - Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 
      200062, P.R. China.
FAU - Xu, Ke
AU  - Xu K
AD  - Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 
      200062, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20201001
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Carrier Proteins)
RN  - 0 (Fatty Acids)
RN  - 0 (Liposomes)
RN  - 0 (Membrane Proteins)
RN  - 0 (Pentacyclic Triterpenes)
RN  - 0 (Thyroid Hormones)
RN  - EC 2.3.1.21 (CPT1A protein, human)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
RN  - EC 6.2.1.3 (ACSL1 protein, human)
RN  - 4G6A18707N (Betulinic Acid)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/*administration & dosage
MH  - Carnitine O-Palmitoyltransferase/antagonists & inhibitors/metabolism
MH  - Carrier Proteins/antagonists & inhibitors/metabolism
MH  - Coenzyme A Ligases/antagonists & inhibitors/metabolism
MH  - Colorectal Neoplasms/*drug therapy/pathology
MH  - Fatty Acids/metabolism
MH  - HCT116 Cells
MH  - Humans
MH  - Liposomes
MH  - Membrane Proteins/antagonists & inhibitors/metabolism
MH  - Nanoparticles/*chemistry
MH  - Pentacyclic Triterpenes/*administration & dosage
MH  - Signal Transduction/drug effects
MH  - Thyroid Hormones/metabolism
MH  - Warburg Effect, Oncologic/*drug effects
MH  - Betulinic Acid
MH  - Thyroid Hormone-Binding Proteins
PMC - PMC7640364
OTO - NOTNLM
OT  - colorectal cancer
OT  - glycolysis
OT  - fatty acid
OT  - betulinic acid
OT  - nanoliposomes
EDAT- 2020/10/31 06:00
MHDA- 2021/08/03 06:00
PMCR- 2020/10/01
CRDT- 2020/10/30 12:09
PHST- 2019/10/24 00:00 [received]
PHST- 2020/06/03 00:00 [accepted]
PHST- 2020/10/31 06:00 [pubmed]
PHST- 2021/08/03 06:00 [medline]
PHST- 2020/10/30 12:09 [entrez]
PHST- 2020/10/01 00:00 [pmc-release]
AID - or-44-06-2595 [pii]
AID - 10.3892/or.2020.7787 [doi]
PST - ppublish
SO  - Oncol Rep. 2020 Dec;44(6):2595-2609. doi: 10.3892/or.2020.7787. Epub 2020 Oct 1.