FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4377093047> ?p ?o ?g. }

• W4377093047 abstract "Glioblastomas are a highly aggressive cancer type which respond poorly to current pharmaceutical treatments, thus novel therapeutic approaches need to be investigated. One such approach involves the use of the bioactive natural product Tanshinone IIA (T2A) derived from the Chinese herb Danshen, where mechanistic insight for this anti-cancer agent is needed to validate its use. Here, we employ a tractable model system, Dictyostelium discoideum, to provide this insight. T2A potently inhibits cellular proliferation of Dictyostelium, suggesting molecular targets in this model. We show that T2A rapidly reduces phosphoinositide 3 kinase (PI3K) and protein kinase B (PKB) activity, but surprisingly, the downstream complex mechanistic target of rapamycin complex 1 (mTORC1) is only inhibited following chronic treatment. Investigating regulators of mTORC1, including PKB, tuberous sclerosis complex (TSC), and AMP-activated protein kinase (AMPK), suggests these enzymes were not responsible for this effect, implicating an additional molecular mechanism of T2A. We identify this mechanism as the increased expression of sestrin, a negative regulator of mTORC1. We further show that combinatory treatment using a PI3K inhibitor and T2A gives rise to a synergistic inhibition of cell proliferation. We then translate our findings to human and mouse-derived glioblastoma cell lines, where both a PI3K inhibitor (Paxalisib) and T2A reduces glioblastoma proliferation in monolayer cultures and in spheroid expansion, with combinatory treatment significantly enhancing this effect. Thus, we propose a new approach for cancer treatment, including glioblastomas, through combinatory treatment with PI3K inhibitors and T2A." @default.
• W4377093047 created "2023-05-20" @default.
• W4377093047 creator A5018847810 @default.
• W4377093047 creator A5023909682 @default.
• W4377093047 creator A5034500617 @default.
• W4377093047 creator A5047168527 @default.
• W4377093047 creator A5062803373 @default.
• W4377093047 creator A5063582138 @default.
• W4377093047 creator A5087930370 @default.
• W4377093047 date "2023-05-19" @default.
• W4377093047 modified "2023-10-10" @default.
• W4377093047 title "Enhanced Sestrin expression through Tanshinone 2A treatment improves PI3K-dependent inhibition of glioma growth" @default.
• W4377093047 cites W100933412 @default.
• W4377093047 cites W1965165221 @default.
• W4377093047 cites W1969067003 @default.
• W4377093047 cites W1980181290 @default.
• W4377093047 cites W1987182404 @default.
• W4377093047 cites W2007403037 @default.
• W4377093047 cites W2010077871 @default.
• W4377093047 cites W2013206354 @default.
• W4377093047 cites W2018434780 @default.
• W4377093047 cites W2027778493 @default.
• W4377093047 cites W2031941651 @default.
• W4377093047 cites W2042423862 @default.
• W4377093047 cites W2057366353 @default.
• W4377093047 cites W2064146837 @default.
• W4377093047 cites W2069258667 @default.
• W4377093047 cites W2079172266 @default.
• W4377093047 cites W2085328713 @default.
• W4377093047 cites W2089520086 @default.
• W4377093047 cites W2095927835 @default.
• W4377093047 cites W2101935092 @default.
• W4377093047 cites W2107674876 @default.
• W4377093047 cites W2109816625 @default.
• W4377093047 cites W2119151792 @default.
• W4377093047 cites W2119856985 @default.
• W4377093047 cites W2159664830 @default.
• W4377093047 cites W2164675211 @default.
• W4377093047 cites W2271605574 @default.
• W4377093047 cites W2287443485 @default.
• W4377093047 cites W2419226942 @default.
• W4377093047 cites W2464198273 @default.
• W4377093047 cites W2549463549 @default.
• W4377093047 cites W2593816418 @default.
• W4377093047 cites W2614794838 @default.
• W4377093047 cites W2744377419 @default.
• W4377093047 cites W2791115421 @default.
• W4377093047 cites W2806731973 @default.
• W4377093047 cites W2809128264 @default.
• W4377093047 cites W2809375380 @default.
• W4377093047 cites W2888539040 @default.
• W4377093047 cites W2890480133 @default.
• W4377093047 cites W2893895555 @default.
• W4377093047 cites W2896869836 @default.
• W4377093047 cites W2908338174 @default.
• W4377093047 cites W2908505739 @default.
• W4377093047 cites W2940228483 @default.
• W4377093047 cites W2942151559 @default.
• W4377093047 cites W2970489971 @default.
• W4377093047 cites W2972471297 @default.
• W4377093047 cites W2986630158 @default.
• W4377093047 cites W2989299979 @default.
• W4377093047 cites W2993217589 @default.
• W4377093047 cites W2997706148 @default.
• W4377093047 cites W2998469527 @default.
• W4377093047 cites W2999607433 @default.
• W4377093047 cites W3002440776 @default.
• W4377093047 cites W3005712859 @default.
• W4377093047 cites W3005900314 @default.
• W4377093047 cites W3015501897 @default.
• W4377093047 cites W3083080034 @default.
• W4377093047 cites W3094885259 @default.
• W4377093047 cites W3118203090 @default.
• W4377093047 cites W3137233412 @default.
• W4377093047 cites W3144288344 @default.
• W4377093047 cites W3147646302 @default.
• W4377093047 cites W3159148096 @default.
• W4377093047 cites W3162903074 @default.
• W4377093047 cites W3164860903 @default.
• W4377093047 cites W3165709262 @default.
• W4377093047 cites W3178774309 @default.
• W4377093047 cites W3179843219 @default.
• W4377093047 cites W3181245501 @default.
• W4377093047 cites W3182150311 @default.
• W4377093047 cites W3183870607 @default.
• W4377093047 cites W3186706039 @default.
• W4377093047 cites W3198933552 @default.
• W4377093047 cites W3210306676 @default.
• W4377093047 cites W3215478200 @default.
• W4377093047 cites W3217143594 @default.
• W4377093047 cites W4200223581 @default.
• W4377093047 cites W4206594101 @default.
• W4377093047 cites W4207081653 @default.
• W4377093047 cites W4251526733 @default.
• W4377093047 doi "https://doi.org/10.1038/s41420-023-01462-6" @default.
• W4377093047 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37202382" @default.
• W4377093047 hasPublicationYear "2023" @default.
• W4377093047 type Work @default.
• W4377093047 citedByCount "0" @default.
• W4377093047 crossrefType "journal-article" @default.

• next