Mitochondrial potassium channels, such as ATP-regulated or large conductance Ca2+ -activated and voltage gated channels were implicated in cytoprotective phenomenon in different tissues. Basic effects of these channels activity include changes in mitochondrial matrix volume, mitochondrial respiration and membrane potential, and generation of reactive oxygen species. In this paper, we describe the pharmacological properties of mitochondrial potassium channels and their modulation by channel inhibitors and potassium channel openers. We also discuss potential side effects of these substances.

A soluble complement inhibitor factor H (FH) and its splice variant factor H-like protein (FHL) have been recently discovered to play a major role in malignant cell escape from complement-mediated cytotoxicity in lung-, ovarian-and glia-derived neoplasms. The role of FH in colon cancer has not yet been examined. Here, we studied immunocytochemically FH/FHL expression in tumor samples derived from 40 patients, with both primary colon adenocarcinoma and metastatic foci in the liver. FH/FHL immunoreactivity was present in stroma of both primary and metastatic tumors, in virtually all patients. The cellular immunoreactivity was observed infrequently. Importantly, when analyzed quantitatively, FH/FHL immunoreactivity was significantly increased in liver metastases when compared with the primary sites. In addition, we have analyzed FH and FHL expression in 5 colon cancer cell lines: SW480, SW620, HCT116, HT-29 and Lovo. FH mRNA and FH secretion were observed in SW620 and HT-29 cells, whereas FHL was produced only by HT-29 cell-line. By confocal and electron microscopy, FH immunoreactivity was associated with the plasma membrane and intracellular vesicular structures. Finally, we have analyzed the role of FH in the susceptibility of SW620 colon cancer cells to complement-mediated damage. When FH function was blocked, using specific antibody, the cells became more susceptible to lysis. Taken together, our results suggest an important role of FH/FHL in colon cancer cells defense against complement-mediated cytotoxicity, and in metastatic process. ' 2008 Wiley-Liss, Inc.Key words: factor H; colon cancer; metastasis; immunotherapy; complement Although recent years have brought many advances in clinical oncology, colon cancer is still a serious problem. Surgical resection remains as the most efficient treatment, but its results are often not satisfactory. Sixty percent of patients with colon cancer develop liver metastases, which, for a third of those, is the main and only metastatic site. About 25% of the patients have potentially resectable hepatic metastases, but at least half of them have recurrence after surgery. 1 Unfortunately, for a large group of patients, radical surgery is impossible. For about 60% of such patients, advanced chemo-and radiotherapy allows for a 5-year survival, however a major objection to this kind of treatment is severe side effects. 2 To improve disease-free survival, overall survival and to prevent formation of metastases, new strategies for effective treatment should be considered.