Back to Search
Start Over
Chemical compounds that suppress hypoxia-induced stress granule formation enhance cancer drug sensitivity of human cervical cancer HeLa cells
- Source :
- The Journal of Biochemistry. 164:381-391
- Publication Year :
- 2018
- Publisher :
- Oxford University Press (OUP), 2018.
-
Abstract
- In eukaryotic cells, when exposed to certain types of stress including hypoxia, eIF2α is phosphorylated by several kinases including protein kinase R (PKR) and PKR-like endoplasmic reticulum kinase (PERK). Subsequently, protein translation is stopped and stress granules (SGs) are formed. Cancer cells form SGs under hypoxia. SGs accumulate apoptosis-related molecules and play anti-apoptotic roles. Thus, hypoxia-induced SG formation contributes to drug resistance in cancer cells. For this reason, inhibition of SG formation is expected to be beneficial in cancer therapy. To prove this concept, chemical reagents that inhibit SG formation are required as experimental tools. We searched for chemical compounds that suppress SG formation and identified that β-estradiol, progesterone, and stanolone (hereafter described as EPS) inhibit SG formation in human cervical cancer HeLa cells. As it turned out, EPS block PKR but not PERK, thus fail to suppress SG formation in most cancer cells, where SGs are formed via PERK. Nevertheless, in this study, we used HeLa cells as a model and demonstrated that EPS block hypoxia-induced SG formation in HeLa cells and consequently reduce drug resistance that HeLa cells acquire under hypoxia. Our findings support that inhibition of SG formation is a useful method to control cancers.
- Subjects :
- 0301 basic medicine
Cell Survival
Drug Evaluation, Preclinical
Antineoplastic Agents
Biochemistry
HeLa
03 medical and health sciences
0302 clinical medicine
Stress granule
Humans
Hypoxia
Protein kinase A
Molecular Biology
Progesterone
Cell Proliferation
Estradiol
biology
Cell growth
Kinase
Chemistry
Endoplasmic reticulum
Dihydrotestosterone
General Medicine
Endoplasmic Reticulum Stress
biology.organism_classification
Protein kinase R
Cell biology
030104 developmental biology
030220 oncology & carcinogenesis
Cancer cell
Drug Screening Assays, Antitumor
HeLa Cells
Subjects
Details
- ISSN :
- 17562651 and 0021924X
- Volume :
- 164
- Database :
- OpenAIRE
- Journal :
- The Journal of Biochemistry
- Accession number :
- edsair.doi.dedup.....f108d7857cc24711ca66623685610db5