國家衛生研究院 NHRI:Item 3990099045/12612

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12612

Title:	Betulinic acid-mediated tuning of PERK/CHOP signaling by Sp1 inhibition as a novel therapeutic strategy for glioblastoma
Authors:	Lo, WL;Hsu, TI;Yang, WB;Kao, TJ;Wu, MH;Huang, YN;Yeh, SH;Chuang, JY
Contributors:	Institute of Biotechnology and Pharmaceutical Research;NHRI Graduate Student Program
Abstract:	Patients with glioblastoma are at high risk of local recurrences after initial treatment with standard therapy, and recurrent tumor cells appear to be resistant to first-line drug temozolomide. Thus, finding an effective second-line agent for treating primary and recurrent glioblastomas is critical. Betulinic acid (BA), a natural product of plant origin, can cross the blood–brain barrier. Here, we investigated the antitumor effects of BA on typical glioblastoma cell lines and primary glioblastoma cells from patients, as well as corresponding temozolomide-resistant cells. Our findings verified that BA significantly reduced growth in all examined cells. Furthermore, gene-expression array analysis showed that the unfolded-protein response was significantly affected by BA. Moreover, BA treatment increased activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C/EBP homologous protein (CHOP) apoptotic pathway, and reduced specificity protein 1 (Sp1) expression. However, Sp1 overexpression reversed the observed cell-growth inhibition and PERK/CHOP signaling activation induced by BA. Because temozolomide-resistant cells exhibited significantly increased Sp1 expression, we concluded that Sp1-mediated PERK/CHOP signaling inhibition protects glioblastoma against cancer therapies; hence, BA treatment targeting this pathway can be considered as an effective therapeutic strategy to overcome such chemoresistance and tumor relapse.
Date:	2020-04-15
Relation:	Cancers. 2020 Apr 15;12(4):Article number 981.
Link to:	http://dx.doi.org/10.3390/cancers12040981
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2072-6694&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000535587400209
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85083825139
Appears in Collections:	[Shiu-Hwa Yeh] Periodical Articles [Others] Periodical Articles

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