Lactoferrin-induced apoptosis and PLD activation in oral squamous cell carcinoma cell line

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In the present study, I examined biological mechanisms of apoptosis induced by pepsin hydrolyzed-lactoferrin (lactoferricin) in oral squamous cell carcinoma cell lines.【RESULTS】The treatment of oral cancer cells with pepsin-digested lactoferrin caused changes as followed.1) Suppressed |3H|thymidine incorporation.2) Induced condensation of chromatin stained by Hoechst 33258.3) Induced the fragmentation of DNA.4) Increased the leak of intracellular LDH.5) Increased ERK protein phosphorylation (=activations).6) Elongated serum-induced ERK, JNK protein phosphorylation.7) Stimulated PLD activation.8) Suppressed mRNA expression of PKC ε and η isozymes【Conclusion】In this study, we found that lactoferricin peptides, produced by acid-pepsin hydrolysis of bovine lactoferrin, induced cell death involving apoptotic nuclear change in human oral squamous cell carcinoma cell lines. At early stage of apoptosis, the treatment of lactoferricin induced activations of ERK, and PLD and prolonged serum-induced activations of ERK and JNK at later stage (24-27 hrs). Moreover, 6hrs treatment of lactoferricin peptides decreased mRNA expression levels of protein kinase Cε and η isozymes. These changes of signaling enzymes may play a role in apoptotic process of oral cancer cells induced by lactoferricin peptides.