Chemical compounds that suppress hypoxia-induced stress granule formation enhance cancer drug sensitivity of human cervical cancer HeLa cells

Journal of Biochemistry
Shikshya TimalsinaYutaka Hata

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...Continue Reading

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Citations

Mar 30, 2019·Life Science Alliance·Alexander Martin HeberleKathrin Thedieck
Mar 6, 2019·Cell Death & Disease·Ruiqi WangJin Xu
Jul 18, 2020·Cell Stress & Chaperones·Naki A AdjirackorSimon C Harvey
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Aug 31, 2021·International Journal of Cancer. Journal International Du Cancer·Debmita Chatterjee, Oishee Chakrabarti

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