Supporting InformationS1 Stelliosphaerol A (1) 1 H NMR (600 MHz, CD 3 OD) S2 Stelliosphaerol A (1) 13 C NMR (150 MHz, CD 3 OD)S17 Agar-based Growth Inhibition Assay S18 Liquid Culture Growth Inhibition Assay S19 Growth Optimization Experiment S20 EM Photomicrographs S21-S24 Organisms and DNA Loci used in Phylogenetic Analysis S25 Phylogenetic Distance Analysis S26-S27 Supplemental Phylogeny S28 Supplemental Methods S29 References S1 Stelliosphaerol A (1) 1 H NMR (600 MHz, CD 3 OD) S2 Stelliosphaerol A (1) 13 C NMR (150 MHz, CD 3 OD) S3 Stelliosphaerol A (1) gCOSY (CD 3 OD) S4 Stelliosphaerol A (1) gCOSY of polyl moeity (CD 3 OD) S5 Stelliosphaerol A (1) gHSQC (CD 3 OD) S6 Stelliosphaerol A (1) gHMBC (CD 3 OD) S7 Stelliosphaerol A (1) ROESY (CD 3 OD) S8 Stelliosphaerol A (1) ROESY-expansion (CD 3 OD) S9 Stelliosphaerol A (1) ROESY (acetone-d6) S10 Stelliosphaerol A(1) HRESIMS (+) S11 Stelliosphaerol B (2) 1 H NMR (600 MHz, CD 3 OD) S12 Stelliosphaerol B (2) 13 C NMR (150 MHz, CD 3 OD) S13 Stelliosphaerol B (2) gCOSY (CD 3 OD) S14 Stelliosphaerol B (2) gHSQC (CD 3 OD) S15 Stelliosphaerol B (2) gHMBC (CD 3 OD) S16 Stelliosphaerol B (2) HRESIMS (+) S17 Agar-based Growth Inhibition Assay Crude extracts of isolate E11018A (Stelliosphaera formicum) were re-suspended in MeOH to final concentrations of 58.6 mg/mL (CH 2 Cl 2 extract) and 143.2 mg/mL (EtOAc extract), and 5 µL aliquots were applied to a lawn of Staphylococcus aureus. The upper left quadrant, MeOH control; upper right quadrant, CH 2 Cl 2 extract; lower right quadrant, EtOAc extract; lower left quadrant, no treatment.
Renal or kidney cancer accounts for about 3% of all cancer cases reported each year in the US. Molecular signatures that define the cancer, such as the loss of functional VHL, are found in both sporadic and familial cases of cancer. In clear cell renal cancer, the transcription factor HIF-2α has been shown to have a distinct role in tumorigenesis. Our laboratories developed a cell-based screen to identify modulators of HIF-2α. Screening of the NCI's Natural Product Extract Repository resulted in the identification of 10 sponge extracts from which 12 compounds were isolated. The biological evaluation of these compounds will be discussed including evaluation of HIF-1α vs. HIF-2αselectively and the isolated compounds' effects on mRNA from several pathways regulated by HIF.Approximately 58,000 individuals were diagnosed with renal cell carcinoma (RCC, kidney cancer) in 2011, 1 accounting for 3% of the cancers in the USA. 2 RCC is not a single disease, but can be separated into several distinct diseases based on clinical, morphological and molecular features. Many of these molecular features have been identified based on the study of families that are affected by inherited renal cancer syndromes. 2 Certain molecular features of patients with Von Hippel Lindau (VHL) disease are also present in individuals who develop sporadic clear cell RCC, the most prevalent RCC subtype. 3 Specifically, loss of VHL gene function as occurs in Von Hippel Lindau patients is seen in > 90% of sporadic RCC tumors. VHL protein (pVHL) is part of an E3 ubiquitin ligase system that recognizes and marks substrates for degradation. 4 The primary substrate of the pVHL complex is hypoxia inducible factor-alpha subunit (HIF-α). There are three known isoforms of HIF-α: * Corresponding Author: Tel: (301) 846-1943. Fax: (301) Under normal levels of oxygen, specific proline residues in HIF-1α and HIF-2α are hydroxylated. This reaction allows VHL to bind and ubiquitylate the α-subunit leading to its degradation. Under hypoxic conditions, this hydroxylation does not take place, HIF-α subunits accumulate within the cell, dimerize with ARNT, and translocate to the nucleus where they bind to hypoxia response elements (HREs), turning on transcription of a large number of genes. HIF regulated genes function in a variety of pathways including angiogenesis (e.g., vascular endothelial growth factor, VEGF), cell survival (e.g., erythropoietin, EPO) and glucose metabolism (e.g., glucose transporter-1, GLUT1) that together allow the cell to cope with and survive under the hypoxic conditions. 5 It is therefore not surprising that HIF has been shown to be upregulated in many tumors due to intratumoral hypoxia or by genetic mutation. Indeed upregulation of HIF is often associated with aggressive growth, treatment resistance, metastasis, and poor prognosis. 6 In renal cancer, HIF-2α plays a primary role in tumorigenesis. [7][8][9] To better understand the importance of HIF-2α to RCC, our laboratories generated a cellbased screen to identify inhibitors of HIF...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.