Searching across hundreds of databases
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs. Metformin bound to the active-site heme of CYP3A4 in a co-crystal structure, establishing CYP3A4 as a biguanide target. Structure-based design led to discovery of N1-hexyl-N5-benzyl-biguanide (HBB), which bound to the CYP3A4 heme with higher affinity than metformin. HBB potently and specifically inhibited CYP3A4 AA epoxygenase activity. HBB also inhibited growth of established ER+ mammary tumors and suppressed intratumoral mTOR. CYP3A4 AA epoxygenase inhibition by biguanides thus demonstrates convergence between eicosanoid activity in mitochondria and biguanide action in cancer, opening a new avenue for cancer drug discovery.
Pubmed ID: 28919040 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This site is designed for researchers and students who want a quick way to generate random numbers or assign participants to experimental conditions. Research Randomizer can be used in a wide variety of situations, including psychology experiments, medical trials, and survey research. The program uses a JavaScript random number generator to produce customized sets of random numbers. Since its release in 1997, Research Randomizer has been used to generate number sets over 10.7 million times. This service is part of Social Psychology Network and is fast, free, and runs with any recent web browser as long as JavaScript isn''t disabled. Research Randomizer is a free service offered to students and researchers interested in conducting random assignment and random sampling. By using this service, you agree to abide by the SPN User Policy and to hold Research Randomizer and its staff harmless in the event that you experience a problem with the program or its results. Although every effort has been made to develop a useful means of generating random numbers, Research Randomizer and its staff do not guarantee the quality or randomness of numbers generated. Any use to which these numbers are put remains the sole responsibility of the user who generated them. What are the system requirements needed to run Research Randomizer? This program works best with Firefox and other recent web browsers. If you''re using a browser that came with America Online, or older browsers made prior to 2003, you may experience some difficulties with Research Randomizer. You may also not be able to use Research Randomizer with some limited-function browsers that do not fully support JavaScript, such as the Opera broswer used on certain game consoles. We would suggest that you update to a fairly recent, fully- functional stand-alone browser. How do I know what browser I am using? The easiest way to find this out is to click Help on the pulldown menu at the top of the screen. One of the options should be About Mozilla Firefox, About Internet Explorer, About Netscape, or something similar. Selecting this option will open a window that displays the name, version number, and copyright date of your browser. How does Research Randomizer generate its numbers? Research Randomizer uses the Math.random method within the JavaScript programming language to generate its random numbers for all modern web browsers. If you are using an older version of Microsoft Internet Explorer or Netscape Navigator (that is prior to version 4.0 of either), Research Randomizer uses an adaptation of the Central Randomizer by Paul Houle. Note that Research Randomizer no longer supports much-older browsers by other vendors (e.g., Mosaic). Who designed Research Randomizer? The original idea and programming for Research Randomizer came from Geoffrey C. Urbaniak in 1997. Research Randomizer was then jointly developed with Scott Plous, webmaster of Social Psychology Network, and online tutorials were added to the main program. In 1999 the site was redesigned with the assistance of Mike Lestik, in 2003 Mike Lestik added the download function, and in 2007 Mike Lestik and Scott Plous redesigned the site and added new content.
View all literature mentionsSoftware to manage Seahorse XFe24 Analyzer, which measures OCR and ECAR of live cells in a 24-well plate format. Users can create and modify assay templates and analyze and manage data.
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis polyclonal targets SQSTM1/p62
View all literature mentionsThis monoclonal targets Beclin-1
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThis monoclonal targets Stat3
View all literature mentionsThis monoclonal targets Phospho-Stat3 (Tyr705)
View all literature mentionsThis polyclonal targets AMPK-alpha
View all literature mentionsThis monoclonal targets Phospho-AMPK (Thr172) (D79.5E) Rabbit mAb
View all literature mentionsThis polyclonal targets p70 S6 Kinase
View all literature mentionsThis polyclonal targets Phospho-p70 S6 Kinase (Thr389)
View all literature mentionsThis unknown targets mTOR
View all literature mentionsThis monoclonal targets Phospho-mTOR (Ser2448)
View all literature mentionsCell line T-47D is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
