Summary of Study ST001732

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001108. The data can be accessed directly via it's Project DOI: 10.21228/M8GM5B This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST001732
Study Title	Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance (part-III)
Study Summary	Chemotherapy remains the standard of care for most cancers worldwide, however development of chemoresistance due to the presence of the drug-effluxing ABC transporters remains a significant problem. The development of safe and effective means to overcome chemoresistance is critical for achieving durable remissions in many cancer patients. We have investigated the energetic demands of ABC transporters in the context of the metabolic adaptations of chemoresistant cancer cells. Here we show that ABC transporters use mitochondrial-derived ATP as a source of energy to efflux drugs out of cancer cells. We further demonstrate that the loss of MCJ (DnaJC15), an endogenous negative regulator of mitochondrial respiration, in chemoresistant cancer cells boosts their ability to produce ATP from mitochondria and fuel ABC transporters. We have developed novel MCJ mimetics that can attenuate mitochondrial respiration and safely overcome chemoresistance in vitro and in vivo. Administration of MCJ mimetics in combination with standard chemotherapeutic drugs could therefore become an new strategy for treatment of multiple cancers.
Institute	University of Colorado Anschutz Medical Campus
Department	Biochemistry and Molecular Genetics
Laboratory	Angelo D'Alessandro
Last Name	Culp-Hill
First Name	Rachel
Address	12801 E 17th Ave L18-9403D
Email	rachel.hill@cuanschutz.edu
Phone	3037245798
Submit Date	2021-03-18
Raw Data Available	Yes
Raw Data File Type(s)	raw(Thermo)
Analysis Type Detail	LC-MS
Release Date	2021-03-31
Release Version	1

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Treatment:

Treatment ID:	TR001822
Treatment Summary:	Cells were cultured under normal conditions, detached using trypsin-EDTA (0.05 %), counted, normalized to 0.5 x 106 in each sample, and then cell pellets were snap frozen in liquid nitrogen prior to analysis. To determine the effect of N-MCJ mimetic treatment, equal numbers of NCI/ADR-RES cells were plated and allowed grow for 2 d followed by the addition of vehicle or MITOx30 (25 μM) for 12 h. Cells were then collected and processed as above.

Treatment ID:

TR001822

Treatment Summary:

Cells were cultured under normal conditions, detached using trypsin-EDTA (0.05 %), counted, normalized to 0.5 x 106 in each sample, and then cell pellets were snap frozen in liquid nitrogen prior to analysis. To determine the effect of N-MCJ mimetic treatment, equal numbers of NCI/ADR-RES cells were plated and allowed grow for 2 d followed by the addition of vehicle or MITOx30 (25 μM) for 12 h. Cells were then collected and processed as above.