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361.
Emilie Jaune Elisa Cavazza Cyril Ronco Oleksandr Grytsai Patricia Abbe Nedra Tekaya Marwa Zerhouni Guillaume Beranger Lisa Kaminski Frdric Bost Maeva Gesson Meri Tulic Paul Hofman Robert Ballotti Thierry Passeron Thomas Botton Rachid Benhida Stphane Rocchi 《Cell death & disease》2021,12(1)
In the search of biguanide-derived molecules against melanoma, we have discovered and developed a series of bioactive products and identified the promising new compound CRO15. This molecule exerted anti-melanoma effects on cells lines and cells isolated from patients including the ones derived from tumors resistant to BRAF inhibitors. Moreover, CRO15 was able to decrease viability of cells lines from a broad range of cancer types. This compound acts by two distinct mechanisms. First by activating the AMPK pathway induced by a mitochondrial disorder. Second by inhibition of MELK kinase activity, which induces cell cycle arrest and activation of DNA damage repair pathways by p53 and REDD1 activation. All of these mechanisms activate autophagic and apoptotic processes resulting in melanoma cell death. The strong efficacy of CRO15 to reduce the growth of melanoma xenograft sensitive or resistant to BRAF inhibitors opens interesting perspective.Subject terms: Melanoma, Cell death 相似文献
362.
M P Grilli A Capucci P Rocchi 《Bollettino della Società italiana di biologia sperimentale》1982,58(24):1679-1684
Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line eue at a very low frequency (8 x 10(-6)). We have studied in this system the effect of the promoting agent phorbol-12-myristate-13-acetate (TPA) on mutagenesis induced by benzo(a)pyrene (BP). TPA did not increase the mutation frequencies induced by BP, but it showed a trend to make shorter the expression time. 相似文献
363.
M Gobbo L Biondi F Filira R Rocchi 《International journal of peptide and protein research》1991,38(5):417-427
The glyco-hexapeptide sequence H-Val-(GalNAc-alpha)Thr-His-Pro-Gly-Tyr-OH, was synthesized in solution by the segment condensation procedure and the stepwise procedure. A peracetylated, O-galactosaminyl threonine derivative was used for incorporating the glycosylated amino acid residue into the peptide chain. A consistent racemization occurred during the acylation of H-His-Pro-Gly-Tyr(Bzl)-OBzl with Z-Val-[GalNAc(Ac)3-alpha]Thr-OH by the BOP-HOBt procedure and the D-allothreonine containing glyco-hexapeptide was isolated in about 20% yield. Stepwise elongation of the C-terminal tetrapeptide with Fmoc-[GalNAc(Ac)3-alpha]Thr-OH and Z-Val-OH, in the presence of the same coupling reagents, yielded the L-threonine containing diastereoisomer without detectable racemization. A side product, the Nim-ethoxycarbonylated hexapeptide derivative, formed during the EEDQ-mediated condensation of Fmoc-[GalNAc(Ac)3-alpha]Thr-OH with the C-terminal tetrapeptide, was isolated and characterized. Preliminary studies showed that the synthetic glycohexapeptide is a good competitive inhibitor of the binding of the FDC-6 monoclonal antibody to the oncofetal fibronectin, supporting the idea that it should represent the minimum essential structure required for the FDC-6 activity. 相似文献