SemOpenAlex |

SemOpenAlex

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387035257> ?p ?o ?g. }

Showing items 1 to 100 of ±122 with 100 items per page.

W4387035257 abstract "Abstract Objectives Growing evidence indicates that pancreatic cancer stem cells (CSCs) contribute to cancer recurrence via chemoresistance, and their growth is sustained by self-renewal. Targeting the self-renewal of pancreatic CSCs is a crucial strategy to eradicate them. Here, we are the first to describe a known KRAS inhibitor, 4,6-dichloro-2-methyl-3-aminoethyl-indole (DCAI), as a novel anti-pancreatic CSC agent that abrogates the self-renewal of pancreatic CSCs. Methods Cell viability assay was used to determine the cytotoxicity of KRAS binders in pancreatic cancer cell lines with either wild-type KRAS (BxPC-3) or clinically relevant KRAS mutations (PANC-1, Capan-2, and MIA PaCa-2). The tumoursphere assay was utilised to investigate the effect of DCAI on the self-renewal of pancreatic CSCs, and its mechanism of action was examined by Western blotting. Results The growth of pancreatic cancer cells remains unaffected by the binding of Benzimidazole (BZIM) to both wild-type and oncogenic KRAS. DCAI and Kobe0065 were equally potent in pancreatic cancer cell lines, except for Capan-2, in which DCAI (GI 50 =25.8 ± 0.8 µM) was more potent than Kobe0065 (GI 50 =54.0 ± 1.0 µM). Capan-2 tumourspheres were markedly irresponsive to gemcitabine (IC 50 >100 µM), while DCAI abrogated the formation of Capan-2 tumourspheres profoundly (IC 50 =30 µM). Upon treatment with DCAI, CRAF, ERK1, ERK2, and AKT activations were significantly inhibited, and SOX2 expression was greatly reduced in Capan-2 tumourspheres. Conclusions Our present study revealed that DCAI depletes pancreatic CSCs by inhibiting self-renewal via KRAS–CRAF–ERK1/2–SOX2 and KRAS–AKT–SOX2 axes. Our findings suggested that KRAS is a valid therapeutic target in pancreatic CSCs for eradicating cancer recurrence." @default.
W4387035257 created "2023-09-27" @default.
W4387035257 creator A5011702824 @default.
W4387035257 creator A5061411213 @default.
W4387035257 creator A5077637212 @default.
W4387035257 creator A5081285661 @default.
W4387035257 creator A5083438015 @default.
W4387035257 creator A5088387922 @default.
W4387035257 date "2023-09-27" @default.
W4387035257 modified "2023-09-27" @default.
W4387035257 title "More than just a KRAS inhibitor: DCAI abrogates the self-renewal of pancreatic cancer stem cells <i>in vitro</i>" @default.
W4387035257 cites W1892036645 @default.
W4387035257 cites W1908612571 @default.
W4387035257 cites W1964173135 @default.
W4387035257 cites W1986034385 @default.
W4387035257 cites W2011805324 @default.
W4387035257 cites W2012479646 @default.
W4387035257 cites W2029572050 @default.
W4387035257 cites W2054786727 @default.
W4387035257 cites W2097606117 @default.
W4387035257 cites W2108002446 @default.
W4387035257 cites W2114273672 @default.
W4387035257 cites W2119028086 @default.
W4387035257 cites W2124111260 @default.
W4387035257 cites W2130251290 @default.
W4387035257 cites W2146926552 @default.
W4387035257 cites W2270139959 @default.
W4387035257 cites W2284961166 @default.
W4387035257 cites W2308164225 @default.
W4387035257 cites W2947108723 @default.
W4387035257 cites W2947424432 @default.
W4387035257 cites W2968665721 @default.
W4387035257 cites W2972602909 @default.
W4387035257 cites W2981521201 @default.
W4387035257 cites W2996690712 @default.
W4387035257 cites W3006012565 @default.
W4387035257 cites W3047475137 @default.
W4387035257 cites W3087617819 @default.
W4387035257 cites W3088838661 @default.
W4387035257 cites W3111685565 @default.
W4387035257 cites W3159037839 @default.
W4387035257 cites W3192755399 @default.
W4387035257 cites W3195264720 @default.
W4387035257 cites W3198590238 @default.
W4387035257 cites W3205527665 @default.
W4387035257 cites W4206779370 @default.
W4387035257 cites W4221005208 @default.
W4387035257 cites W4221040819 @default.
W4387035257 cites W4226065164 @default.
W4387035257 cites W4285589389 @default.
W4387035257 cites W4286219973 @default.
W4387035257 cites W4296460616 @default.
W4387035257 cites W4297973493 @default.
W4387035257 cites W4310533885 @default.
W4387035257 cites W4312209949 @default.
W4387035257 cites W4323857131 @default.
W4387035257 doi "https://doi.org/10.1515/oncologie-2023-0214" @default.
W4387035257 hasPublicationYear "2023" @default.
W4387035257 type Work @default.
W4387035257 citedByCount "0" @default.
W4387035257 crossrefType "journal-article" @default.
W4387035257 hasAuthorship W4387035257A5011702824 @default.
W4387035257 hasAuthorship W4387035257A5061411213 @default.
W4387035257 hasAuthorship W4387035257A5077637212 @default.
W4387035257 hasAuthorship W4387035257A5081285661 @default.
W4387035257 hasAuthorship W4387035257A5083438015 @default.
W4387035257 hasAuthorship W4387035257A5088387922 @default.
W4387035257 hasBestOaLocation W43870352571 @default.
W4387035257 hasConcept C121608353 @default.
W4387035257 hasConcept C126322002 @default.
W4387035257 hasConcept C185592680 @default.
W4387035257 hasConcept C2780210213 @default.
W4387035257 hasConcept C2780258809 @default.
W4387035257 hasConcept C2781187634 @default.
W4387035257 hasConcept C28328180 @default.
W4387035257 hasConcept C502942594 @default.
W4387035257 hasConcept C526805850 @default.
W4387035257 hasConcept C53227056 @default.
W4387035257 hasConcept C54355233 @default.
W4387035257 hasConcept C55427017 @default.
W4387035257 hasConcept C55493867 @default.
W4387035257 hasConcept C62112901 @default.
W4387035257 hasConcept C71924100 @default.
W4387035257 hasConcept C81885089 @default.
W4387035257 hasConcept C86803240 @default.
W4387035257 hasConcept C95444343 @default.
W4387035257 hasConceptScore W4387035257C121608353 @default.
W4387035257 hasConceptScore W4387035257C126322002 @default.
W4387035257 hasConceptScore W4387035257C185592680 @default.
W4387035257 hasConceptScore W4387035257C2780210213 @default.
W4387035257 hasConceptScore W4387035257C2780258809 @default.
W4387035257 hasConceptScore W4387035257C2781187634 @default.
W4387035257 hasConceptScore W4387035257C28328180 @default.
W4387035257 hasConceptScore W4387035257C502942594 @default.
W4387035257 hasConceptScore W4387035257C526805850 @default.
W4387035257 hasConceptScore W4387035257C53227056 @default.
W4387035257 hasConceptScore W4387035257C54355233 @default.
W4387035257 hasConceptScore W4387035257C55427017 @default.
W4387035257 hasConceptScore W4387035257C55493867 @default.
W4387035257 hasConceptScore W4387035257C62112901 @default.