Version 1
: Received: 18 May 2023 / Approved: 18 May 2023 / Online: 18 May 2023 (08:31:34 CEST)
How to cite:
Miyata, S.; Ishii, T.; Kitanaka, S. 3EE, 20Ac-Ingenol Decreases HIF-1α/PD-L1 through ATR Activation under Hypoxia and Induces Apoptosis in Panc-1 Cells Accumulating Cyclin D1. Preprints2023, 2023051300. https://doi.org/10.20944/preprints202305.1300.v1
Miyata, S.; Ishii, T.; Kitanaka, S. 3EE, 20Ac-Ingenol Decreases HIF-1α/PD-L1 through ATR Activation under Hypoxia and Induces Apoptosis in Panc-1 Cells Accumulating Cyclin D1. Preprints 2023, 2023051300. https://doi.org/10.20944/preprints202305.1300.v1
Miyata, S.; Ishii, T.; Kitanaka, S. 3EE, 20Ac-Ingenol Decreases HIF-1α/PD-L1 through ATR Activation under Hypoxia and Induces Apoptosis in Panc-1 Cells Accumulating Cyclin D1. Preprints2023, 2023051300. https://doi.org/10.20944/preprints202305.1300.v1
APA Style
Miyata, S., Ishii, T., & Kitanaka, S. (2023). 3EE, 20Ac-Ingenol Decreases HIF-1α/PD-L1 through ATR Activation under Hypoxia and Induces Apoptosis in Panc-1 Cells Accumulating Cyclin D1. Preprints. https://doi.org/10.20944/preprints202305.1300.v1
Chicago/Turabian Style
Miyata, S., Takashi Ishii and Susumu Kitanaka. 2023 "3EE, 20Ac-Ingenol Decreases HIF-1α/PD-L1 through ATR Activation under Hypoxia and Induces Apoptosis in Panc-1 Cells Accumulating Cyclin D1" Preprints. https://doi.org/10.20944/preprints202305.1300.v1
Abstract
Apoptosis under severe hypoxia is induced through p53 phosphorylation and HIF-1α-dependent p53 accumulation via ATR activation by DNA damage response (DDR) activation through replication stress. We previously demonstrated that the topoisomerase I catalytic inhibitor, 3EZ, 20Ac-ingenol, specifically induced apoptosis in Jeko-1 and Panc-1 cells, both of which are cell lines that show cyclin D1 overexpression. After progression to the S phase facilitated by nuclear cyclin D1, in the presence of 3EZ, 20Ac-ingenol, an intra S phase checkpoint was induced in ATR activation as part of replication stress-induced DDR. In this study, we examined whether 3EE, 20Ac-ingenol induces a higher degree of p53 phosphorylation and additional HIF-1α and p53 accumulation in response to replication stress-induced DDR activation under the hypoxic condition than under the normoxic condition by controlling ATR activation. 3EE, 20Ac-ingenol induced p53 activation and HIF-1α-dependent p53 accumulation through cooperative ATR activation via induced DDR with the hypoxia in Panc-1 cells. The Jeko-1 cells showed slight HIF-1α accumulation under hypoxia, but this was not decreased by 3EE, 20Ac-ingenol, so that the cells remained resistant to hypoxia. 3EE, 20Ac-ingenol induces an intricate interplay between p53 and HIF-1α accumulation via ATR activations that results in high p53 accumulation, which advanced transient expression and early disappearance of HIF-1?. The strong p53 accumulation and consequent PTEN activation also decreased HIF-1α accumulation and PD-L1 expression, which resulted in intense apoptosis.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
