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Molecules, Vol. 24, Pages 2012: Cytostatic and Cytotoxic Natural Products against Cancer Cell Models

Molecules 28 May 25

This study outlines a simplified approach to identify lead compounds from natural products against several cancer cell lines, and provides the basis to better understand structure activity relationship of the natural product cephalotaxine. Using high-throughput screening, a natural product library containing fractions and pure compounds was interrogated for proliferation inhibition in acute lymphoblastic leukemia cellular models (SUP-B15 and KOPN-8). Initial hits were verified in control and counter screens, and those with EC50 values ranging from nanomolar to low micromolar were further characterized via mass spectrometry, NMR, and cytotoxicity measurements. Most of the active compounds were alkaloid natural products including cephalotaxine and homoharringtonine, which were validated as protein synthesis inhibitors with significant potency against several cancer cell lines. A generated BODIPY-cephalotaxine probe provides insight into the mode of action of cephalotaxine and further rationale for its weaker potency when compared to homoharringtonine. The steroidal natural products (ecdysone and muristerone A) also showed modest biological activity and protein synthesis inhibition. Altogether, these findings demonstrate that natural products continue to provide insight into structure and function of molecules with therapeutic potential against drug resistant cancer cell models.

ConclusionWe established four distinct stable cell lines expressing firefly luciferase (fLuci) gene by infection of lentivirus in Jurkat, CCRF-CEM, Sup-T1 and CCRF-HSB2 ALL cells. 105 ALL/fLuci cells together with 106 MSCs were inoculated into NOD/SCID mice by intraperitoneal (IP) injection. And we measured luciferase activity using an IVIS optical imaging technique to determine the effects of MSCs on leukemic mass formation. Much higher luciferase activity was observed when ALL/fLuci cells were co-injected with MSCs as compared to that when ALL/fLuci cells were inoculated alone. In addition, we co-inoculated 105 ALL/fLuci...

Publication date: Available online 18 May 2019Source: Cancer GeneticsAuthor(s): Roberto Antonucci, Nadia Vacca, Elisa Ghisu, Gloria Acquaviva, Carlo Cosmi, Anna Maria Marinaro, Cristian Locci, Claudio FozzaAbstractIsodicentric chromosome 15, also called idic(15), is a rare chromosomal abnormality resulting from inverted duplication of proximal 15q. It is associated with specific clinical findings such as early central hypotonia, developmental delay, cognitive dysfunction, autism spectrum disorders, and seizure. Herein we describe a case of a girl with idic(15) syndrome who developed acute lymphoblastic leukemia (ALL) at th...

CONCLUSIONS: We demonstrate that target antigen modulation is a promising strategy to improve CD22 CAR efficacy and remission durability in patients with leukemia and lymphoma. PMID: 31110075 [PubMed - as supplied by publisher]

Isodicentric chromosome 15, also called idic(15), is a rare chromosomal abnormality resulting from inverted duplication of proximal 15q. It is associated with specific clinical findings such as early central hypotonia, developmental delay, cognitive dysfunction, autism spectrum disorders, and seizure. Herein we describe a case of a girl with idic(15) syndrome who developed acute lymphoblastic leukemia (ALL) at the age of 9 years. Our case suggests a possible correlation between idic(15) and ALL, and possible functional links between these two conditions.

Isabel Medina-Vera Sergio Juárez-Méndez Droplet digital PCR is the most robust method for absolute nucleic acid quantification. However, RNA is a very versatile molecule and its abundance is tissue-dependent. RNA quantification is dependent on a reference control to estimate the abundance. Additionally, in cancer, many cellular processes are deregulated which consequently affects the gene expression profiles. In this work, we performed microarray data mining of different childhood cancers and healthy controls. We selected four genes that showed no gene expression variations (PSMB6, PGGT1B, UBQLN2 and ...

Authors: Brown PA, Wieduwilt M, Logan A, DeAngelo DJ, Wang ES, Fathi A, Cassaday RD, Litzow M, Advani A, Aoun P, Bhatnagar B, Boyer MW, Bryan T, Burke PW, Coccia PF, Coutre SE, Jain N, Kirby S, Liu A, Massaro S, Mattison RJ, Oluwole O, Papadantonakis N, Park J, Rubnitz JE, Uy GL, Gregory KM, Ogba N, Shah B Abstract Survival outcomes for older adults with acute lymphoblastic leukemia (ALL) are poor and optimal management is challenging due to higher-risk leukemia genetics, comorbidities, and lower tolerance to intensive therapy. A critical understanding of these factors guides the selection of frontline therapies an...

Childhood acute lymphoblastic leukemia (cALL) is the most frequent pediatric cancer. Over the past decades, treatment of cALL has significantly improved, with cure rates close to 90%. However intensive chemoth...