Hexavalent chromium [Cr(VI)] is a lung carcinogen and its complete mechanism of action remains to be investigated. Metabolic reprogramming of key energy metabolism pathways (e.g., increased anaerobic glycolysis in the presence of oxygen or “Warburg effect,” dysregulated mitochondrial function, and lipogenesis) are important to cancer cell and tumor survival and growth. In our current understanding of Cr(VI)-induced carcinogenesis, the role for metabolic reprogramming remains unclear. In this study, we treated human lung epithelial cells (BEAS-2B) with Cr(VI) for 6 months and obtained malignantly transformed cells from an isolated colony grown in soft agar. We also used Cr(VI)-transformed cells from two other human lung cell lines (BEP2D and WTHBF-6 cells). Overall, we found that all the Cr(VI)-transformed cells had no changes in their mitochondrial respiratory functions (measured by the Seahorse Analyzer) compared with passaged-matched control cells. Using a xenograft tumor growth model, we generated tumors from these transformed cells in Nude mice. Using cells obtained from the xenograft tumor tissues, we observed that these cells had decreased maximal mitochondrial respiration, spare respiratory capacity, and coupling efficiency. These results provide evidence that, although mitochondrial dysfunction does not occur during Cr(VI)-induced transformation of lung cells, it does occur during tumor development.
|Number of pages||13|
|Journal||Journal of Environmental Pathology, Toxicology and Oncology|
|State||Published - 2018|
Bibliographical noteFunding Information:
This work was supported by NIH (Grants R01ES021771, R01ES020870, R01ES025515, R01ES28984, R01ES21771, and P30ES026529) and the Redox Metabolism Shared Resource Facility of the University of Kentucky Markey Cancer Center (Grant P30CA177558).
The authors thank Hong Lin from the University of Kentucky for technical and administrative support. We thank Dr. John P. Wise, Sr., University of Louisville (Louisville, KY), for the use of the WTHBF-6 Cells, and Dr. Curtis Harris, National Institute of Health, for the use of the BEP2D cells. This work was supported by NIH (Grants R01ES021771, R01ES020870, R01ES025515, R01ES28984, R01ES21771, and P30ES026529) and the Redox Metabolism Shared Resource Facility of the University of Kentucky Markey Cancer Center (Grant P30CA177558).
© 2018 by Begell House, Inc.
- Hexavalent chromium
- Seahorse Analyzer
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Health, Toxicology and Mutagenesis