cytochrome-c-t and caffeic-acid

The anti-proliferation effect of caffeic acid (3,4-dihydroxycinnamic acid), isolated from Ocimum gratissimum Linn, on human cervical cancer cells (HeLa cells) was examined to elucidate the associated mechanism and death mode.. Flow cytometry showed that caffeic acid treatment results in dramatically increased apoptosis of HeLa cells. Western blot analysis revealed that caffeic acid activates various processed caspases.. Caffeic acid significantly reduced proliferation of HeLa cells in a concentration-dependent manner. Morphological evidence of apoptosis, including nuclei fragmentation was clearly observed 24 and 48 hours after exposure to caffeic acid (1 mM and 10 mM) by flow cytometry. Time-dependent inhibition was also observed. Caffeic acid decreased levels of uncleaved caspase-3 and Bcl-2, and induced cleaved caspase-3 and p53.. Caffeic acid induces apoptosis by inhibiting Bcl-2 activity, leading to release of cytochrome c and subsequent activation of caspase-3, indicating that caffeic acid induces apoptosis via the mitochondrial apoptotic pathway. This also suggests that caffeic acid has a strong anti-tumor effect and may be a promising chemopreventive or chemotherapeutic agent.

Topics: Apoptosis; Blotting, Western; Caffeic Acids; Caspase 3; Cell Cycle; Cell Proliferation; Cytochromes c; Dose-Response Relationship, Drug; Enzyme Activation; Female; Flow Cytometry; HeLa Cells; Humans; Mitochondria; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Tumor Suppressor Protein p53

It is an important therapeutic strategy to protect mitochondria from oxidative stress, especially during ischemia-reperfusion. In the present study, an attempt has been made to evaluate the protective effects of caffeic acid phenethyl ester (CAPE) and its related phenolic compounds on mouse brain and liver mitochondria injury induced by in vitro anoxia-reoxygenation. Added before anoxia or reoxygenation, CAPE markedly protected coupled respiration with the decrease in state 4 and the increases in state 3, respiratory control ratio (RCR) and ADP/O ratio in a concentration-dependent manner. CAPE effectively protected mitochondria by inhibiting the mitochondrial membranes fluidity decrease, the lipoperoxidation and the protein carbonylation increase, which indicated its protective action against the mitochondrial oxidative damage. Meanwhile, CAPE blocked the enhanced release of cardiolipin (CL) and cytochrome c (Cyt c). The related phenolic compounds like caffeic acid (CA), ferulic acid (FA) and ethyl ferulate (EF) also had different-degree protective effects. CAPE and CA were more potent than FA and EF. Their structural differences played the key role in their activity levels. These results suggest that CAPE and its related phenolic compounds protect mitochondria mainly correlated to their antioxidative activities and may be of interest for the prevention and therapy of ischemia-reperfusion injuries.

Topics: Anaerobiosis; Animals; Anisotropy; Antioxidants; Brain; Caffeic Acids; Coumaric Acids; Cytochromes c; Dose-Response Relationship, Drug; Male; Mice; Mitochondria; Mitochondria, Liver; Mitochondrial Membranes; Molecular Structure; Oxygen; Phenylethyl Alcohol; Thiobarbituric Acid Reactive Substances