Cytochrome c is well known as a carrier of electrons during respiration. Current evidence indicates that
cytochrome c also functions as a major component of
apoptosomes to induce apoptosis in eukaryotic cells as well as an
antioxidant. More recently, a prokaryotic
cytochrome c,
cytochrome c(551) from Pseudomonas aeruginosa, has been shown to enter in mammalian cells such as the murine macrophage-like J774 cells and causes inhibition of cell cycle progression. Much less is known about such functions by mammalian
cytochromes c, particularly the human
cytochrome c. We now report that similar to P. aeruginosa
cytochrome c(551), the purified human
cytochrome c protein can enter J774 cells and induce cell cycle arrest at the G(1) to S phase, as well as at the G(2)/M phase at higher concentrations. Unlike P. aeruginosa
cytochrome c(551) which had no effect on the induction of apoptosis, human
cytochrome c induces significant apoptosis and cell death in J774 cells, presumably through inhibition of the cell cycle at the G(2)/M phase. When incubated with human
breast cancer MCF-7 and normal mammary epithelial cell line MCF-10A1 cells, human
cytochrome c entered in both types of cells but induced cell death only in the normal MCF-10A1 cells. The ability of human
cytochrome c to enter J774 cells was greatly reduced at 4 degrees C, suggesting energy requirement in the entry process.