Double face of cytochrome c in cancers.New look into human breast ducts with Raman imaging

Cytochrome c (Cyt c) is a key protein that is needed to maintain life (respiration) and cell death (apoptosis). The dual-function of Cyt c comes from its capability to act as mitochondrial redox carrier that transfers electrons between the membrane-embedded complexes III and IV and to serve as a cytoplasmic apoptosis-triggering agent, activating the caspase cascade.1-6 However, the precise roles of Cyt c in mitochondria, cytoplasm and extracellular matrix under normal and pathological conditions are not completely understood.7-9 To date, no pathway of Cyt c release that results in caspase activation has been compellingly demon-strated in any invertebrate.10 The significance of mitochondrial dysfunctionality has not been studied in ductal carcinoma to the best of our knowledge.1 Here we show that proper concentration of monounsaturated fatty acids, saturated fatty acids, cardi-olipin and Cyt c is critical in the correct breast ductal functioning and constitutes an important parameter to assess breast epithelial cells integrity and homeostasis. We look inside human breast ducts answering fundamental questions about location and distribution of various biochemical components inside the lumen, epithelial cells of the duct and the extracellular matrix around the cancer duct during cancer development in situ. We found in histopathologically controlled breast cancer duct that Cyt c, cardi-olipin, and palmitic acid are the main components inside the lumen of cancerous duct in situ. The pre-sented results show direct evidence that Cyt c is released to the lumen from the epithelial cells in can-cerous duct. In contrast the lumen in normal duct is empty and free of Cyt c. Our results demonstrate how Cyt c is likely to function in cancer development. We anticipate our results to be a starting point for more sophisticated in vitro and in vivo animal models. For example, the correlation between concentration of Cyt c and cancer grade could be tested in various types of cancer. Furthermore, Cyt c is a target of anti-cancer drug development 11,12 and a well-defined and quantitative Raman based assay for oxidative phosphorylation and apoptosis will be relevant for such developments.