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Noninvasive radiofrequency treatment effect on mitochondria in pancreatic cancer cells
Author(s) -
Curley Steven A.,
Palalon Flavio,
Lu Xiaolin,
Koshkidezhda V.
Publication year - 2014
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28895
Subject(s) - mitochondrion , colocalization , cancer cell , microbiology and biotechnology , autophagy , reactive oxygen species , mitophagy , intracellular , apoptosis , cancer research , pathology , medicine , biology , cancer , biochemistry
BACKGROUND The development of novel therapeutic approaches for cancer therapy is important, especially for tumors that have poor response or develop resistance to standard chemotherapy and radiation. We discovered that noninvasive radiofrequency (RF) fields can affect cancer cells but not normal cells, inhibit progression of tumors in mice, and enhance the anticancer effects of chemotherapy. However, it remains unclear what physiological and molecular mechanisms this treatment induces inside cells. Here, we studied the effect of RF treatment on mitochondria in human pancreatic cancer cells. METHODS The morphology of mitochondria in cells was studied via electron microscopy. The alteration of mitochondrial membrane potential (Δψ) was accessed using a Mitotracker probe. The respiratory activity of mitochondria was evaluated by analyzing changes in oxygen consumption rates determined with a Mito Stress Test Kit. The production of intracellular reactive oxygen species was performed using flow cytometry. The colocalization of mitochondria and autophagosome markers in cells was performed using fluorescence immunostaining and confocal microscopy analysis. RESULTS RF fields treatment changed the morphology of mitochondria in cancer cells, altered polarization of the mitochondrial membrane, substantially impaired mitochondrial respiration, and increased reactive oxygen species production, indicating RF‐induced stress on the mitochondria. We also observed frequent colocalization of the autophagosome marker LC3B with the mitochondrial marker Tom20 inside cancer cells after RF exposure, indicating the presence of mitochondria in the autophagosomes. This suggests that RF‐induced stress can damage mitochondria and induce elimination of damaged organelles via autophagy. CONCLUSION RF treatment impaired the function of mitochondria in cancer cells. Therefore, mitochondria can represent one of the targets of the RF treatment. Cancer 2014;120:3418–3425. © 2014 American Cancer Society .