Biological activity of mistletoe: in vitro and in vivo studies and mechanisms of action

摘要

Mechanism of anticancer activity of mistletoe. Mistletoe targets two important signalling pathways, PI3K/AKT and MAPK. PI3K/AKT pathway is responsible for growth and survival of cancer cells. Mistletoe induces apoptosis by inhibition of AKT phosphorylation. MAPK pathway is mediated by ERK, p38 and JNK. Mistletoe enhances p38 and JNK1 activation and reduces ERK leading to apoptosis and cell cycle arrest of cancer cells. Mistletoe downregulates cyclins (CCND1, CCNE, CCNA) and cyclin-dependent protein kinases (CDK4, CDK2) inhibiting cell cycle. Mistletoe upregulates proapoptotic proteins (Bax) and downregulates inhibitors of apoptosis (IAPs) such as BCL2, BCL2L1, MCL1, XIAP. Furthermore, mistletoe leads to release of cytochrome c and activation of caspases resulting in apoptosis