Ca
Antineoplastic Agents
/ pharmacology
Calcium
/ metabolism
Cell Line, Tumor
Endoplasmic Reticulum
/ drug effects
Humans
Melanoma
/ metabolism
Membrane Potential, Mitochondrial
/ drug effects
Mitochondria
/ drug effects
Mitochondrial Swelling
/ drug effects
Mitogen-Activated Protein Kinases
/ metabolism
Reactive Oxygen Species
/ metabolism
Regulated Cell Death
/ drug effects
Signal Transduction
/ drug effects
Vitamin E
/ analogs & derivatives
Ca2+ overload
Melanoma
Mitochondrial impairment
Paraptosis
ROS production
Tocotrienols
Journal
Apoptosis : an international journal on programmed cell death
ISSN: 1573-675X
Titre abrégé: Apoptosis
Pays: Netherlands
ID NLM: 9712129
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
accepted:
16
03
2021
pubmed:
4
4
2021
medline:
25
12
2021
entrez:
3
4
2021
Statut:
ppublish
Résumé
Melanoma is an aggressive tumor with still poor therapy outcomes. δ-tocotrienol (δ-TT) is a vitamin E derivative displaying potent anti-cancer properties. Previously, we demonstrated that δ-TT triggers apoptosis in human melanoma cells. Here, we investigated whether it might also activate paraptosis, a non-canonical programmed cell death. In accordance with the main paraptotic features, δ-TT was shown to promote cytoplasmic vacuolization, associated with endoplasmic reticulum/mitochondrial dilation and protein synthesis, as well as MAPK activation in A375 and BLM cell lines. Moreover, treated cells exhibited a significant reduced expression of OXPHOS complex I and a marked decrease in oxygen consumption and mitochondrial membrane potential, culminating in decreased ATP synthesis and AMPK phosphorylation. This mitochondrial dysfunction resulted in ROS overproduction, found to be responsible for paraptosis induction. Additionally, δ-TT caused Ca
Identifiants
pubmed: 33811561
doi: 10.1007/s10495-021-01668-y
pii: 10.1007/s10495-021-01668-y
pmc: PMC8197726
doi:
Substances chimiques
Antineoplastic Agents
0
Reactive Oxygen Species
0
Vitamin E
1406-18-4
tocotrienol, delta
1SRB74OWSI
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
277-292Références
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