Different effects of 4β-hydroxywithanolide E and withaferin A, two withanolides from Solanaceae plants, on the Akt signaling pathway in human breast cancer cells.
Antineoplastic Agents, Phytogenic
/ pharmacology
Apoptosis
/ drug effects
Cell Cycle Checkpoints
/ drug effects
Cell Death
/ drug effects
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p21
/ genetics
Female
Humans
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Signal Transduction
/ drug effects
Solanaceae
/ chemistry
Triple Negative Breast Neoplasms
/ drug therapy
Withanolides
/ pharmacology
4β-hydroxywithanolide E
PI3K, Akt
Withaferin A
Withanolides
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
03
08
2017
revised:
02
08
2018
accepted:
03
09
2018
pubmed:
23
1
2019
medline:
16
7
2019
entrez:
23
1
2019
Statut:
ppublish
Résumé
Triple-negative breast cancer (TNBC) represents a clinical challenge because it lacks sensitivity to hormone therapy or other available molecule-targeted agents. In addition, TNBC frequently exhibits over-activation of the PI3K/Akt survival pathway that can contribute to chemotherapy resistance. 4β-Hydroxywithanolide E (4-HW) and withaferin A (WA) are two withanolides from Solanaceae plants that exhibit promising anticancer activity in vitro and in vivo. The aim of this study is to investigate and compare the effects of 4-HW and WA on TNBC cells and underling mechanisms. The anticancer effects of 4-HW and WA were evaluated by cell viability, cell cycle arrest, and apoptosis assays. PI3K/Akt signaling and the expression of survivin, Bcl-2 family proteins and cyclin-dependent kinase inhibitors were evaluated by Western blot. The role of PI3K/Akt signaling in the withanolides-induced anticancer effects was examined by using a PI3K inhibitor and overexpression of a constitutively active form of Akt. In TNBC MDA-MB-231 cells, 4-HW and WA displayed different kinetic effect on cell availability. Cell cycle analysis revealed that 4-HW induced the G The withanolides 4-HW and WA potently inhibit the viability of TNBC cells through induction of cell cycle arrest and apoptosis/necrosis. The PI3K/Akt pathway plays distinct roles in cancer cells respond to 4-HW and WA. These results suggest the potential applications of the withanolides for the treatment of TNBC.
Sections du résumé
BACKGROUND
BACKGROUND
Triple-negative breast cancer (TNBC) represents a clinical challenge because it lacks sensitivity to hormone therapy or other available molecule-targeted agents. In addition, TNBC frequently exhibits over-activation of the PI3K/Akt survival pathway that can contribute to chemotherapy resistance. 4β-Hydroxywithanolide E (4-HW) and withaferin A (WA) are two withanolides from Solanaceae plants that exhibit promising anticancer activity in vitro and in vivo.
PURPOSE
OBJECTIVE
The aim of this study is to investigate and compare the effects of 4-HW and WA on TNBC cells and underling mechanisms.
STUDY DESIGN/METHODS
METHODS
The anticancer effects of 4-HW and WA were evaluated by cell viability, cell cycle arrest, and apoptosis assays. PI3K/Akt signaling and the expression of survivin, Bcl-2 family proteins and cyclin-dependent kinase inhibitors were evaluated by Western blot. The role of PI3K/Akt signaling in the withanolides-induced anticancer effects was examined by using a PI3K inhibitor and overexpression of a constitutively active form of Akt.
RESULTS
RESULTS
In TNBC MDA-MB-231 cells, 4-HW and WA displayed different kinetic effect on cell availability. Cell cycle analysis revealed that 4-HW induced the G
CONCLUSION
CONCLUSIONS
The withanolides 4-HW and WA potently inhibit the viability of TNBC cells through induction of cell cycle arrest and apoptosis/necrosis. The PI3K/Akt pathway plays distinct roles in cancer cells respond to 4-HW and WA. These results suggest the potential applications of the withanolides for the treatment of TNBC.
Identifiants
pubmed: 30668401
pii: S0944-7113(18)30295-2
doi: 10.1016/j.phymed.2018.09.017
pii:
doi:
Substances chimiques
4-hydroxywithanolide E
0
Antineoplastic Agents, Phytogenic
0
CDKN1A protein, human
0
Cyclin-Dependent Kinase Inhibitor p21
0
Withanolides
0
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
withaferin A
L6DO3QW4K5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
213-222Informations de copyright
Copyright © 2018 Elsevier GmbH. All rights reserved.