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HS-146, a novel phosphoinositide 3-kinase alpha inhibitor, induces the apoptosis and inhibits the metastatic ability of human breast cancer cells

DC Field Value Language
dc.contributor.authorOk Hyeon Kim-
dc.contributor.authorJu‑Hee Lee-
dc.contributor.authorShinmee Mah-
dc.contributor.authorSung Yun Park-
dc.contributor.authorSungwoo Hong-
dc.contributor.authorSoon‑Sun Hong-
dc.date.available2020-07-06T06:42:04Z-
dc.date.created2020-06-29-
dc.date.issued2020-06-
dc.identifier.issn1019-6439-
dc.identifier.urihttps://pr.ibs.re.kr/handle/8788114/7122-
dc.description.abstractThe 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 PI3K alpha 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 p21(Waf1/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 3 beta (GSK3 beta), p70S6K1 and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). Hypoxia-inducible factor (HIF)-1 alpha 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 PI3K alpha inhibitor, may be an effective novel therapeutic candidate that suppresses breast cancer proliferation and metastasis by inhibiting the PI3K/Akt/mTOR pathway-
dc.language영어-
dc.publisherSPANDIDOS PUBL LTD-
dc.subjectphosphoinositide 3-kinase alpha inhibitor-
dc.subjectHS-146-
dc.subjectproliferation-
dc.subjectapoptosis-
dc.subjectcell cycle-
dc.subjecthypoxia-
dc.subjectmigration-
dc.subjectinvasion-
dc.titleHS-146, a novel phosphoinositide 3-kinase alpha inhibitor, induces the apoptosis and inhibits the metastatic ability of human breast cancer cells-
dc.typeArticle-
dc.type.rimsART-
dc.identifier.wosid000530403800014-
dc.identifier.scopusid2-s2.0-85082838714-
dc.identifier.rimsid72504-
dc.contributor.affiliatedAuthorShinmee Mah-
dc.contributor.affiliatedAuthorSungwoo Hong-
dc.identifier.doi10.3892/ijo.2020.5018-
dc.identifier.bibliographicCitationINTERNATIONAL JOURNAL OF ONCOLOGY, v.56, no.6, pp.1509 - 1520-
dc.relation.isPartOfINTERNATIONAL JOURNAL OF ONCOLOGY-
dc.citation.titleINTERNATIONAL JOURNAL OF ONCOLOGY-
dc.citation.volume56-
dc.citation.number6-
dc.citation.startPage1509-
dc.citation.endPage1520-
dc.description.journalClass1-
dc.description.journalClass1-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalWebOfScienceCategoryOncology-
dc.subject.keywordPlusSIGNALING PATHWAY-
dc.subject.keywordPlusANTICANCER ACTIVITY-
dc.subject.keywordPlusPI3K PATHWAY-
dc.subject.keywordPlusANGIOGENESIS-
dc.subject.keywordPlusTARGETS-
dc.subject.keywordPlusCYCLE-
dc.subject.keywordAuthorphosphoinositide 3-kinase alpha inhibitor-
dc.subject.keywordAuthorHS-146-
dc.subject.keywordAuthorproliferation-
dc.subject.keywordAuthorapoptosis-
dc.subject.keywordAuthorcell cycle-
dc.subject.keywordAuthorhypoxia-
dc.subject.keywordAuthormigration-
dc.subject.keywordAuthorinvasion-
Appears in Collections:
Center for Catalytic Hydrocarbon Functionalizations(분자활성 촉매반응 연구단) > 1. Journal Papers (저널논문)
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