Radiotherapy, despite its precision and non-invasiveness, often fails due to the resistance of cancer stem cells (CSCs), which are characterized by high self-renewal capabilities and superior DNA repair mechanisms. These cells can evade RT and lead to tumor recurrence and metastasis. To address this challenge, a novel delivery system named PB has been introduced. This system combines liposomes with platelet membranes to encapsulate Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES), thus enhancing its delivery and release specifically at tumor sites. In addition, this system not only targets CSCs effectively but also increases the local concentration of BPTES upon X-ray irradiation, which reduces glutathione levels in tumor cells, thereby increasing oxidative stress and damaging mitochondria. PB-elicited mitochondrial damage as the STING signal initiator, which mediated significant upregulation in the expression of a cGAS-STING pathway-related protein thereby amplifying the STING signal. Systemic intravenous administration of PB remarkably promoted DC maturation and CD8+ T cell infiltration, thus eliciting strong antitumor effects. Overall, this PB system presents a potent method to overcome CSC-related resistance and offers a promising approach for future cancer treatment protocols.

2024-09-01·American Journal of Physiology-Cell Physiology

Glutamine metabolism improves left ventricular function but not macrophage-mediated inflammation following myocardial infarction

Article

作者: Sherrod, Stacy D ; da Silva, Alexandre A ; Morato, Jemylle G ; Stanford, Joshua K. ; Codreanu, Simona G ; Omoto, Ana C ; Morato, Jemylle G. ; do Carmo, Jussara M. ; Omoto, Ana C. M. ; Li, Xuan ; da Silva, Alexandre A. ; Aitken, Nikaela M. ; Sherrod, Stacy D. ; Mouton, Alan J. ; do Carmo, Jussara M ; Schrimpe-Rutledge, Alexandra C. ; Schrimpe-Rutledge, Alexandra C ; Li, Xuan ; McLean, John A ; O’Quinn, Katherine R. ; Stanford, Joshua K ; Hall, John E. ; Hall, John E ; Wang, Zhen ; Brown, Jordan A ; McLean, John A. ; Wang, Zhen ; Aitken, Nikaela M ; Codreanu, Simona G. ; Brown, Jordan A. ; Mouton, Alan J

Glutamine metabolism is altered in both infarct macrophages and the remote left ventricle (LV) following myocardial infarction (MI). Supplemental glutamine improves LV function following MI while inhibiting glutamine metabolism with BPTES worsens LV function. Supplemental glutamine or BPTES does not impact macrophage immunometabolic phenotypes after MI.

2024-08-01·Current Medical Science

Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia

Article

作者: Yang, Ying ; Fu, Xing ; Li, Deng-Ju ; Xiao, Min ; Gu, Jia ; Liu, Tong-Yuan

OBJECTIVEThe metabolic reprogramming of acute myeloid leukemia (AML) cells is a compensatory adaptation to meet energy requirements for rapid proliferation. This study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML cells.METHODSSKM-1 cells (an AML cell line) were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES, a glutaminase inhibitor) or cytarabine. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay, and cell apoptosis and reactive oxygen species (ROS) by flow cytometry. Western blotting was conducted to examine the levels of apoptotic proteins, including cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP). Moreover, the human long noncoding RNA (lncRNA) microarray was used to analyze gene expression after glutamine deprivation, and results were confirmed with quantitative RT-PCR (qRT-PCR). The expression of metallothionein 2A (MT2A) was suppressed using siRNA. Cell growth and apoptosis were further detected by CCK-8 assay and flow cytometry, respectively, in cells with MT2A knockdown.RESULTSGlutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 cells. The lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine deprivation. MT2A knockdown increased apoptosis, while proliferation was not affected in SKM-1 cells. In addition, metformin inhibited cell growth and induced apoptosis in SKM-1 cells. Both glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to cytarabine. Furthermore, the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 cells.CONCLUSIONTargeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

100 项与 BPTES 相关的药物交易

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