The Impact of Icariside II on Human Prostate Cancer Cell Proliferation, Mobility, and Autophagy via PI3K-AKT-mTOR Signaling Pathway.
Antineoplastic Agents, Phytogenic
/ pharmacology
Apoptosis
/ drug effects
Autophagy
/ drug effects
Cell Cycle
/ drug effects
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Dose-Response Relationship, Drug
Flavonoids
/ pharmacology
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Male
Oncogene Protein v-akt
/ drug effects
Phosphatidylinositol 3-Kinases
/ drug effects
Prostatic Neoplasms
/ drug therapy
Signal Transduction
/ drug effects
TOR Serine-Threonine Kinases
/ drug effects
Wound Healing
/ drug effects
PI3K-AKT-mTOR
apoptosis
autophagy
icariside II
prostate cancer
Journal
Drug design, development and therapy
ISSN: 1177-8881
Titre abrégé: Drug Des Devel Ther
Pays: New Zealand
ID NLM: 101475745
Informations de publication
Date de publication:
2020
2020
Historique:
received:
19
06
2020
accepted:
15
08
2020
entrez:
29
10
2020
pubmed:
30
10
2020
medline:
7
8
2021
Statut:
epublish
Résumé
The flavonol glycoside icariside II (ICA II) has been shown to exhibit a range of anti-tumor properties. Herein, we evaluated the impact of ICA II on human prostate cancer cell proliferation, motility, and autophagy, and we further evaluated the molecular mechanisms underlying these effects. We treated DU145 human prostate cancer cells with a range of ICA II doses and then assessed their proliferation via CCK-8 assay, while flow cytometry was used to monitor apoptosis and cell cycle progression. We further utilized wound healing and transwell assays to probe the impact of ICA II on migration and invasion, and assessed autophagy via laser confocal fluorescence microscopy. Western blotting was further utilized to measure LC3-II/I, Beclin-1, P70S6K, PI3K, AKT, mTOR, phospho-AKT, phospho-mTOR, and phospho-P70S6K levels, with qRT-PCR being used to evaluate the expression of specific genes at the mRNA level. We found that ICA II was capable of mediating the dose- and time-dependent suppression of DU145 cell proliferation, causing these cells to enter a state of cell cycle arrest and apoptosis. We further determined that ICA II treatment was associated with significant impairment of prostate cancer cell migration and invasion, whereas autophagy was enhanced in treated cells relative to untreated controls. Our results indicate that ICA II treatment is capable of suppressing human prostate tumor cell proliferation and migration while enhancing autophagy via modulating the PI3K-AKT-mTOR signaling pathway. As such, ICA II may be an ideal candidate drug for the treatment of prostate cancer.
Identifiants
pubmed: 33116405
doi: 10.2147/DDDT.S268524
pii: 268524
pmc: PMC7549881
doi:
Substances chimiques
Antineoplastic Agents, Phytogenic
0
Flavonoids
0
baohuoside I
113558-15-9
MTOR protein, human
EC 2.7.1.1
Oncogene Protein v-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4169-4178Informations de copyright
© 2020 Li et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
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