Novel Lobophorins Inhibit Oral Cancer Cell Growth and Induce Atf4- and Chop-Dependent Cell Death in Murine Fibroblasts

 

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Detalles Bibliográficos
Autores: Cruz, Patricia G., Fribley, Andrew M., Miller, Justin R., Larsen, Martha J., Schultz, Pamela J., Jacob, Renju T., Tamayo Castillo, Giselle, Kaufman, Randal J., Sherman, David H.
Formato: artículo original
Fecha de Publicación:2015
Descripción:As part of the International Cooperative Biodiversity Groups (ICBG) Program, we were interested in identifying biologically active unfolded protein response (UPR) inducing compounds from marine microorganisms isolated from Costa Rican biota. With this aim in mind we have now generated more than 33,000 unique prefractionated natural product extracts from marine and terrestrial organisms that have been submitted to the Center of Chemical Genomics (CCG) at the University of Michigan for high throughput screening (HTS). An effective complementary cell-based assay to identify novel modulators of UPR signaling was used for screening extracts. Active fractions were iteratively subjected to reverse-phase HPLC chromatographic analysis, and together with lobophorin A, B, E, and F (1–4), three new lobophorin congeners, designated as CR1 (5), CR2 (6), and CR3 (7) were isolated. Herein, we report that secondary assays revealed that the new lobophorins induced UPR-associated gene expression, inhibited oral squamous cell carcinoma cell growth, and led to UPR-dependent cell death in murine embryonic fibroblast (MEF) cells.
País:Kérwá
Institución:Universidad de Costa Rica
Repositorio:Kérwá
OAI Identifier:oai:https://www.kerwa.ucr.ac.cr:10669/76886
Acceso en línea:https://pubs.acs.org/doi/10.1021/acsmedchemlett.5b00127
https://hdl.handle.net/10669/76886
Access Level:acceso abierto
Palabra clave:Anticancer
ATF4
CHOP
ER stress
Lobophorin
Natural products
Oral cancer
Oral squamous cell carcinoma
UPR