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Luteolin attenuates cancer cell stemness in PTX-resistant oesophageal cancer cells through mediating SOX2 protein stability.
- Source :
-
Pharmacological research [Pharmacol Res] 2021 Dec; Vol. 174, pp. 105939. Date of Electronic Publication: 2021 Oct 14. - Publication Year :
- 2021
-
Abstract
- Cancer drug resistance is a formidable obstacle that enhances cancer stem-like cell properties, tumour metastasis and relapse. Luteolin (Lut) is a natural flavonoid with strong antitumor effects. However, the underlying mechanism(s) by which Lut protects against paclitaxel-resistant (PTX-resistant) cancer cell remains unknown. Herein, we found that Lut significantly attenuated the stem-like properties of PTX-resistant cancer cells by downregulating the expression of SOX2 protein. Additionally, further study showed that Lut could inhibit the PI3K/AKT pathway to decrease the phosphorylation level of AKT(S473) and UBR5 expression, which is an ubiquitin E3 ligase that promotes SOX2 degradation. In addition, Lut also inhibited PTX-resistant cancer cell migration and invasion by blocking epithelial-mesenchymal transition (EMT). Importantly, Lut inhibited the tumorigenic ability of oesophageal PTX-resistant cancer cells and showed no obvious toxicity in vivo. Thus, Lut has potential as a promising agent for drug-resistant oesophageal cancer therapy.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents pharmacology
Cell Line, Tumor
Drug Resistance, Neoplasm drug effects
Esophageal Neoplasms genetics
Esophageal Neoplasms metabolism
Esophageal Neoplasms pathology
Female
Humans
Luteolin pharmacology
Mice, Inbred BALB C
Mice, Nude
Neoplastic Stem Cells drug effects
Paclitaxel pharmacology
Paclitaxel therapeutic use
Phosphatidylinositol 3-Kinases metabolism
Protein Stability drug effects
Proto-Oncogene Proteins c-akt metabolism
SOXB1 Transcription Factors genetics
SOXB1 Transcription Factors metabolism
Mice
Antineoplastic Agents therapeutic use
Esophageal Neoplasms drug therapy
Luteolin therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1096-1186
- Volume :
- 174
- Database :
- MEDLINE
- Journal :
- Pharmacological research
- Publication Type :
- Academic Journal
- Accession number :
- 34655772
- Full Text :
- https://doi.org/10.1016/j.phrs.2021.105939