PubMed Health⌕ Search

Biomedical subjects

R Moorehead

Publications and source records attributed to R Moorehead.

4 recordsLinked to original sources
PubMed1997

Mitochondrial contributions to cancer cell physiology: redox balance, cell cycle, and drug resistance.

Alterations in the biochemistry of mitochondria have been associated with cell transformation and the acquisition of drug resistance to certain chemotherapeutic agents, suggesting that mitochondria may play a supportive role for the cancer cell phenotype. Mitochondria are multifunctional organelles that contribute to the cellular adenosine triphosphate (ATP) pool and cellular redox balance through the production of reactive oxygen intermediates (ROI). Our laboratory has focused on these mitochondrial functions in the context of cancer cell physiology to evaluate the potential role of mitochondria as controllers of tumour cell proliferation. Low concentrations of ROI have been implicated as messengers in intracellular signal transduction mechanisms; thus an imbalance of ROI production from the mitochondria may support cancer cell growth. In addition, suppression of mitochondrial ATP production can halt cell cycle progression at two energetic checkpoints, suggesting that the use of tumor-selective agents to reduce ATP production may offer a therapeutic target for cancer growth control.

Antineoplastic Agents↗
PubMed1993

Mitochondrial alterations in photodynamic therapy-resistant cells.

The characterization of radiation-induced fibrosarcoma cells (RIF-8A) which have been selected for resistance to Photofrin-mediated photodynamic therapy (PDT) is detailed in this report. Morphological and functional assessment of mitochondria in both the resistant RIF-8A and parental RIF-1 cells show distinct differences. Electron micrographs show that the mitochondria in the RIF-8A cells are relatively smaller; stain more densely, and display a higher cristae density than RIF-1 cells. P. A. Andrews et al. (Cancer Res., 52: 1895-1901, 1992) reported similar mitochondrial differences between a human ovarian carcinoma cell line, 2008, and its cisplatin-resistant counterpart (C13*). Dose-response curves demonstrate that these cisplatin-resistant C13* cells show cross-resistance to Photofrin-mediated PDT. Functionally, the RIF-8A cells produce more ATP and demonstrate higher succinate dehydrogenase activity than do the RIF-1 cells, but the rates of oxygen consumption do not differ between the two cell types. The PDT-sensitive RIF-1 cells demonstrate a significantly higher susceptibility to inhibition of glycolytic activity as determined by 2-deoxy-d-glucose survival curves. These findings suggest differences in the efficacy and/or mode(s) of energy production in the RIF-1 and RIF-8A cells. Since mitochondria are sensitive targets for porphyrin-mediated PDT, the observed changes in mitochondrial structure and/or function may be involved in the PDT resistance seen in RIF-8A cells.

Adenosine Triphosphate↗
PubMed1992

Mitochondrial DNA damage by anticancer agents.

Mitochondrial DNA (mtDNA) is susceptible to damage by a number of anticancer agents either directly or indirectly. This damage is of little consequence if only a few of the mtDNA molecules are damaged. However, multiple drug treatments could result in a significant effect on a cell's ability to survive. The differential effect of anticancer agents on either organ specific toxicities or selective tumor kill can be partially accounted for by differential mtDNA content of cells and on the basis of differential protective mechanisms within mitochondria of various organs or tumor tissue. The concept of damage to mitochondria, especially its genome, is a subject of active investigation in various laboratories. This area of research may provide mechanism(s) by which organ specific toxicities or tumor specific toxicities may be elaborated. Also, the concept of targeting tumor specific mitochondria and/or mtDNA by anticancer agents is very attractive but has not come to fruition due to a lack of understanding of the regulation of the genome in tumor cells. Future investigations in this arena will enhance our knowledge on the interaction between anticancer agents and extranuclear DNA.

Animals↗