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Pivotal Role of Iron Homeostasis in the Induction of Mitochondrial Apoptosis by 6-Gingerol Through PTEN Regulated PD-L1 Expression in Embryonic Cancer Cells.
- Source :
- Frontiers in Oncology; 11/3/2021, Vol. 11, p1-12, 12p
- Publication Year :
- 2021
-
Abstract
- Embryonic cancer stem cells (CSCs) can differentiate into any cancer type. Targeting CSCs with natural compounds is a promising approach as it suppresses cancer recurrence with fewer adverse effects. 6-Gingerol is an active component of ginger, which exhibits well-known anti-cancer activities. This study determined the mechanistic aspects of cell death induction by 6-gingerol. To analyze cellular processes, we used Western blot and real-time qPCR for molecular signaling studies and conducted flow cytometry. Our results suggested an inhibition of CSC marker expression and Wnt/β-catenin signaling by 6-gingerol in NCCIT and NTERA-2 cells. 6-Gingerol induced reactive oxygen species generation, the DNA damage response, cell cycle arrest, and the intrinsic pathway of apoptosis in embryonic CSCs. Furthermore, 6-gingerol inhibited iron metabolism and induced PTEN, which both played vital roles in the induction of cell death. The activation of PTEN resulted in the inhibition of PD-L1 expression through PI3K/AKT/p53 signaling. The induction of PTEN also mediated the downregulation of microRNAs miR-20b, miR-21, and miR-130b to result in PD-L1 suppression by 6-gingerol. Hence, 6-gingerol may be a promising candidate to target CSCs by regulating PTEN-mediated PD-L1 expression. [ABSTRACT FROM AUTHOR]
- Subjects :
- GINGER
CANCER cells
PROGRAMMED death-ligand 1
EMBRYONIC stem cells
CANCER stem cells
Subjects
Details
- Language :
- English
- ISSN :
- 2234943X
- Volume :
- 11
- Database :
- Complementary Index
- Journal :
- Frontiers in Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 153420029
- Full Text :
- https://doi.org/10.3389/fonc.2021.781720