Resveratrol Derivative, Trans-3, 5, 4'-Trimethoxystilbene Sensitizes Osteosarcoma Cells to Apoptosis via ROS-Induced Caspases Activation.
Animals
Apoptosis
/ drug effects
Apoptosis Regulatory Proteins
/ metabolism
Caspases
/ metabolism
Cell Line, Tumor
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Osteosarcoma
/ metabolism
Poly (ADP-Ribose) Polymerase-1
/ metabolism
Proto-Oncogene Proteins
/ metabolism
Reactive Oxygen Species
/ metabolism
Resveratrol
/ analogs & derivatives
Stilbenes
/ pharmacology
TNF-Related Apoptosis-Inducing Ligand
/ pharmacology
Tumor Suppressor Protein p53
/ metabolism
Journal
Oxidative medicine and cellular longevity
ISSN: 1942-0994
Titre abrégé: Oxid Med Cell Longev
Pays: United States
ID NLM: 101479826
Informations de publication
Date de publication:
2021
2021
Historique:
received:
23
09
2020
revised:
20
01
2021
accepted:
10
03
2021
entrez:
9
4
2021
pubmed:
10
4
2021
medline:
22
5
2021
Statut:
epublish
Résumé
Numerous studies have shown that resveratrol can induce apoptosis in cancer cells. Trans-3, 5, 4'-trimethoxystilbene (TMS), a novel derivative of resveratrol, is a more potent anticancer compound than resveratrol and can induce apoptosis in cancer cells. Herein, we examined the mechanisms involved in TMS-mediated sensitization of human osteosarcoma (143B) cells to TNF-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis. Our results showed that cotreatment with TSM and TRAIL activated caspases and increased PARP-1 cleavage in 143B cells. Decreasing cellular ROS levels using NAC reversed TSM- and TRAIL-induced apoptosis in 143B cells. NAC abolished the upregulated expression of PUMA and p53 induced by treatment with TRAIL and TSM. Silencing the expression of p53 or PUMA using RNA interference attenuated TSM-mediated sensitization of 143B cells to TRAIL-induced apoptosis. Knockdown of Bax also reversed TSM-induced sensitization of 143B cell to TRAIL-mediated apoptotic cell death. These results indicate that cotreatment with TRAIL and TSM evaluated intracellular ROS level, promoted DNA damage, and activated the Bax/PUMA/p53 pathway, leading to activation of both mitochondrial and caspase-mediated apoptosis in 143B cells. Orthotopic implantation of 143B cells in mice also demonstrated that cotreatment with TRAIL and TSM reversed resistance to apoptosis in cells without obvious adverse effects in normal cells.
Identifiants
pubmed: 33833855
doi: 10.1155/2021/8840692
pmc: PMC8018847
doi:
Substances chimiques
3,4',5-trimethoxystilbene
0
Apoptosis Regulatory Proteins
0
BBC3 protein, human
0
Proto-Oncogene Proteins
0
Reactive Oxygen Species
0
Stilbenes
0
TNF-Related Apoptosis-Inducing Ligand
0
TNFSF10 protein, human
0
Tumor Suppressor Protein p53
0
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Caspases
EC 3.4.22.-
Resveratrol
Q369O8926L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8840692Informations de copyright
Copyright © 2021 Yu Feng et al.
Déclaration de conflit d'intérêts
The authors declare that there is no conflict of interests regarding the publication of this paper.
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