論文 - 詳細
| RRC ID | 70167 |
|---|---|
| 著者 | Fujii T, Kamishikiryo J, Morita T. |
| タイトル | Palbociclib regulates intracellular lipids in mammary tumor cells by secreting lipoprotein lipase. |
| ジャーナル | Pharmacol Rep |
| Abstract |
BACKGROUND:Lipoprotein metabolism is essential for the growth and proliferation of cancer cells, and is involved in the supply of energy and cellular components. Lipoprotein lipase (LPL) is a very important enzyme in lipoprotein metabolism; however, the details underlying the mechanism of LPL secretion are unclear. Palbociclib is an antitumor drug that inhibits cell cycle progression and suppresses the growth of cancer cells. The effects of palbociclib on energy metabolism, particularly on lipid metabolism, have not been fully elucidated. METHODS:We examined the regulation of LPL secretion, which is primarily involved in lipoprotein metabolism. FM3A mouse mammary tumor cells, which are hormone receptor-positive breast cancer cells, were treated with palbociclib, and the activity and protein levels of secreted LPL were measured. Moreover, the changes in intracellular lipid content were measured by fluorescence staining using Nile Red. RESULTS:FM3A cells were treated with palbociclib, the activity and protein content of secreted LPL were increased. The stimulatory secretion of LPL by palbociclib was suppressed by an intracellular Ca2+ chelator (BAPTA-AM) and a Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) inhibitor (STO-609). Furthermore, the palbociclib-stimulated secretion of LPL was not observed in AMP-activated protein kinase (AMPK)-knockdown cells. An increase in the fluorescence intensity of Nile Red was observed in palbociclib-treated cells; however, no increase was observed in LPL-knockdown cells. CONCLUSIONS:Our data suggest that palbociclib causes intracellular lipid accumulation in breast cancer cells by stimulating Ca2+/CaMKK/AMPK-mediated LPL secretion. |
| 巻・号 | 74(3) |
| ページ | 503-512 |
| 公開日 | 2022-6-1 |
| DOI | 10.1007/s43440-022-00365-0 |
| PII | 10.1007/s43440-022-00365-0 |
| PMID | 35366749 |
| MeSH | AMP-Activated Protein Kinases Animals Breast Neoplasms* / drug therapy Calcium-Calmodulin-Dependent Protein Kinase Kinase Female Humans Lipids Lipoprotein Lipase* / metabolism Lipoproteins Mice Piperazines Pyridines |
| IF | 2.761 |
| リソース情報 | |
| ヒト・動物細胞 | FM3A(RCB0086) |