Polyamine stimulation perturbs intracellular Ca2+ homeostasis and decreases viability of breast cancer BT474 cells
| Autor: | King-Chuen Wu, Yuk-Man Leung, Kar-Lok Wong, Louis W C Chow, Lian-Ru Shiao |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cell Survival
Spermidine Spermine Breast Neoplasms General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Polyamines Putrescine Extracellular Homeostasis Humans Cell Proliferation 030304 developmental biology 0303 health sciences Endoplasmic Reticulum Stress Cell biology Gene Expression Regulation Neoplastic chemistry 030220 oncology & carcinogenesis Cancer cell Calcium Female Cyclopiazonic acid Polyamine Receptors Calcium-Sensing Intracellular |
| Zdroj: | Zeitschrift für Naturforschung C. 75:65-73 |
| ISSN: | 1865-7125 0939-5075 |
| DOI: | 10.1515/znc-2019-0119 |
| Popis: | Intracellular polyamines such as spermine and spermidine are essential to cell growth in normal and especially in cancer cells. However, whether extracellular polyamines affect cancer cell survival is unknown. We therefore examined the actions of extracellular polyamines on breast cancer BT474 cells. Our data showed that spermine, spermidine, and putrescine decreased cell viability by apoptosis. These polyamines also elicited Ca2+ signals, but the latter were unlikely triggered via Ca2+-sensing receptor (CaSR) as BT474 cells have been demonstrated previously to lack CaSR expression. Spermine-elicited Ca2+ response composed of both Ca2+ release and Ca2+ influx. Spermine caused a complete discharge of the cyclopiazonic acid (CPA)-sensitive Ca2+ pool and, expectedly, endoplasmic reticulum (ER) stress. The Ca2+ influx pore opened by spermine was Mn2+-impermeable, distinct from the CPA-triggered store-operated Ca2+ channel, which was Mn2+-permeable. Spermine cytotoxic effects were not due to oxidative stress, as spermine did not trigger reactive oxygen species formation. Our results therefore suggest that spermine acted on a putative polyamine receptor in BT474 cells, causing cytotoxicity by Ca2+ overload, Ca2+ store depletion, and ER stress. |
| Databáze: | OpenAIRE |
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