Fisetin and 5-fluorouracil: Effective combination for PIK3CA-mutant colorectal cancer.
Animals
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Class I Phosphatidylinositol 3-Kinases
/ genetics
Colorectal Neoplasms
/ drug therapy
Drug Synergism
Flavonoids
/ administration & dosage
Flavonols
Fluorouracil
/ administration & dosage
HCT116 Cells
HT29 Cells
Humans
Mice
Mutation
Phosphorylation
/ drug effects
Signal Transduction
/ drug effects
Xenograft Model Antitumor Assays
PIK3CA
5-fluorouracil
PI3K/AKT/mTOR signaling
colorectal cancer
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 12 2019
01 12 2019
Historique:
received:
12
10
2018
revised:
12
04
2019
accepted:
17
04
2019
pubmed:
25
4
2019
medline:
1
2
2020
entrez:
25
4
2019
Statut:
ppublish
Résumé
The normal colon epithelium is transformed into its neoplastic counterpart through a series of genetic alterations in driver genes including activating mutations in PIK3CA. Treatment often involves surgery followed by 5-fluorouracil (5-FU) based therapy, which has limited efficiency and serious side effects. We sought to determine whether fisetin, a dietary flavonoid, alone or in combination with 5-FU affected tumorigenesis in the mammalian intestine. We first determined the effect of fisetin, 5-FU or their combination on PIK3CA-mutant and PIK3CA wild-type colon cancer cells by assessing cell viability, colony formation, apoptosis and effects on PI3K/AKT/mTOR signaling. Treatment of PIK3CA-mutant cells with fisetin and 5-FU reduced the expression of PI3K, phosphorylation of AKT, mTOR, its target proteins, constituents of mTOR signaling complex and this treatment increased the phosphorylation of AMPKα. We then determined whether fisetin and 5-FU together or singly affected tumorigenesis in Apc
Identifiants
pubmed: 31018249
doi: 10.1002/ijc.32367
pmc: PMC7465634
mid: NIHMS1563848
doi:
Substances chimiques
Flavonoids
0
Flavonols
0
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CA protein, human
EC 2.7.1.137
fisetin
OO2ABO9578
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3022-3032Subventions
Organisme : NCI NIH HHS
ID : P30 CA014520
Pays : United States
Informations de copyright
© 2019 UICC.
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