HS-146, a novel phosphoinositide 3-kinase α inhibitor, induces the apoptosis and inhibits the metastatic ability of human breast cancer cells
DC Field | Value | Language |
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dc.contributor.author | Kim O.H. | - |
dc.contributor.author | Lee J.-H. | - |
dc.contributor.author | Mah S. | - |
dc.contributor.author | Park S.Y. | - |
dc.contributor.author | Hong S. | - |
dc.contributor.author | Hong S.-S. | - |
dc.date.accessioned | 2021-06-18T07:20:10Z | - |
dc.date.available | 2021-06-18T07:20:10Z | - |
dc.date.issued | 2020-06 | - |
dc.identifier.issn | 1019-6439 | - |
dc.identifier.issn | 1791-2423 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/44486 | - |
dc.description.abstract | The phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in human cancer as it regulates critical cellular functions, such as survival, proliferation and metabolism. In the present study, a novel PI3Kα inhibitor (HS-146) was synthesized and its anticancer effects on MCF-7, MDA-MB-231, SKBR3 and BT-474 human breast cancer cell lines were confirmed. HS-146 was found to be most effective in inhibiting the proliferation of MCF-7 cells and in inducing cell cycle arrest in the G0/G1 phase by downregulating cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)2 and Cdk4, and upregulating p21Waf1/Cip1 protein levels in this cell line. The induction of apoptosis by HS-146 was confirmed by DAPI staining and western blot analysis. Cell shrinkage and nuclear condensation, which are typical morphological markers of apoptosis, were increased by HS-146 in the MCF-7 cells in a concentration-dependent manner, and HS-146 also increased the protein expression levels of cleaved poly(ADP-ribose) polymerase (PARP) and decreased the protein expression levels of Mcl-1 and caspase-7. In addition, HS-146 effectively decreased the phosphorylation levels of downstream PI3K effectors, such as Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β), p70S6K1 and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). Hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression were also suppressed by HS-146 under hypoxic conditions, and HS-146 inhibited the migration and invasion of MCF-7 cells in a concentration-dependent manner. On the whole, the findings of the present study suggest that HS-146, a novel PI3Kα inhibitor, may be an effective novel therapeutic candidate that suppresses breast cancer proliferation and metastasis by inhibiting the PI3K/Akt/mTOR pathway. © 2020 Spandidos Publications. All rights reserved. | - |
dc.format.extent | 12 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Spandidos Publications | - |
dc.title | HS-146, a novel phosphoinositide 3-kinase α inhibitor, induces the apoptosis and inhibits the metastatic ability of human breast cancer cells | - |
dc.type | Article | - |
dc.identifier.doi | 10.3892/ijo.2020.5018 | - |
dc.identifier.bibliographicCitation | International Journal of Oncology, v.56, no.6, pp 1509 - 1520 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000530403800014 | - |
dc.identifier.scopusid | 2-s2.0-85082838714 | - |
dc.citation.endPage | 1520 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 1509 | - |
dc.citation.title | International Journal of Oncology | - |
dc.citation.volume | 56 | - |
dc.type.docType | Article | - |
dc.publisher.location | 그리이스 | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordAuthor | Cell cycle | - |
dc.subject.keywordAuthor | HS-146 | - |
dc.subject.keywordAuthor | Hypoxia | - |
dc.subject.keywordAuthor | Invasion | - |
dc.subject.keywordAuthor | Migration | - |
dc.subject.keywordAuthor | Phosphoinositide 3-kinase α inhibitor | - |
dc.subject.keywordAuthor | Proliferation | - |
dc.subject.keywordPlus | caspase 7 | - |
dc.subject.keywordPlus | cyclin D1 | - |
dc.subject.keywordPlus | cyclin dependent kinase 2 | - |
dc.subject.keywordPlus | cyclin dependent kinase 4 | - |
dc.subject.keywordPlus | cyclin E | - |
dc.subject.keywordPlus | glycogen synthase kinase 3beta | - |
dc.subject.keywordPlus | hs 146 | - |
dc.subject.keywordPlus | hypoxia inducible factor 1alpha | - |
dc.subject.keywordPlus | initiation factor 4E | - |
dc.subject.keywordPlus | mammalian target of rapamycin | - |
dc.subject.keywordPlus | nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase | - |
dc.subject.keywordPlus | phosphatidylinositol 3 kinase inhibitor | - |
dc.subject.keywordPlus | protein kinase B | - |
dc.subject.keywordPlus | protein mcl 1 | - |
dc.subject.keywordPlus | protein p21 | - |
dc.subject.keywordPlus | S6 kinase | - |
dc.subject.keywordPlus | unclassified drug | - |
dc.subject.keywordPlus | vasculotropin | - |
dc.subject.keywordPlus | antineoplastic activity | - |
dc.subject.keywordPlus | apoptosis | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | breast cancer | - |
dc.subject.keywordPlus | BT-474 cell line | - |
dc.subject.keywordPlus | cancer cell | - |
dc.subject.keywordPlus | cancer inhibition | - |
dc.subject.keywordPlus | cell invasion | - |
dc.subject.keywordPlus | cell migration | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | down regulation | - |
dc.subject.keywordPlus | drug effect | - |
dc.subject.keywordPlus | drug synthesis | - |
dc.subject.keywordPlus | G1 phase cell cycle checkpoint | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | human cell | - |
dc.subject.keywordPlus | MCF-7 cell line | - |
dc.subject.keywordPlus | MDA-MB-231 cell line | - |
dc.subject.keywordPlus | priority journal | - |
dc.subject.keywordPlus | protein expression | - |
dc.subject.keywordPlus | protein phosphorylation | - |
dc.subject.keywordPlus | SK-BR-3 cell line | - |
dc.subject.keywordPlus | staining | - |
dc.subject.keywordPlus | Western blotting | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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