Podophyllotoxin reduces the aggressiveness of human oral squamous cell carcinoma through myeloid cell leukemia‑1.
apoptosis
mitochondrial membrane potential
myeloid cell leukemia‑1
oral squamous cell carcinoma
podophyllotoxin
proteasomal degradation
Journal
International journal of molecular medicine
ISSN: 1791-244X
Titre abrégé: Int J Mol Med
Pays: Greece
ID NLM: 9810955
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
18
05
2023
accepted:
05
09
2023
medline:
18
9
2023
pubmed:
15
9
2023
entrez:
15
9
2023
Statut:
ppublish
Résumé
Podophyllotoxin (PPT), which is derived from the podophyllum plant, exhibits marked cytotoxic effects against cancer cells; however, the precise molecular mechanism underlying its activity against human oral squamous cell carcinoma (OSCC) has not been elucidated. In the present study, the mechanism by which PPT induced cytotoxicity in two OSCC cell lines, HSC3 and HSC4, was determined. The effects of PPT on cytotoxicity in HSC3 and HSC4 cells were analyzed using Annexin V/PI double staining, Sub‑G1 analysis, soft agar assays, western blotting, and quantitative PCR. The changes in the mitochondrial membrane potential were assessed using a JC‑1 assay and cytosolic and mitochondrial fractionation. A myeloid cell leukemia‑1 (Mcl‑1) overexpression cell lines were also established to study the role of Mcl‑1 on apoptosis. The results showed that PPT inhibited the growth of the two human OSCC cell lines and induced apoptosis, which was accompanied by mitochondrial membrane depolarization. Compared with the control, PPT reduced the expression of Mcl‑1 in both cell lines through a proteasome‑dependent protein degradation process. Overall, these results suggested that targeting of Mcl‑1 protein by PPT induced apoptosis, providing a foundation for further pre‑clinical and clinical study of its value in the management of OSCC.
Identifiants
pubmed: 37711052
doi: 10.3892/ijmm.2023.5306
pii: 103
pmc: PMC10619536
doi:
pii:
Substances chimiques
Podophyllotoxin
L36H50F353
Myeloid Cell Leukemia Sequence 1 Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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