Korean mistletoe lectin-induced apoptosis in hepatocarcinoma cells is associated with inhibition of telomerase via mitochondrial controlled pathway independent of p53

The extract of European mistletoe (Viscum album, L) has been used in adjuvant chemotherapy of cancer and mistletoe lectins are considered to be major active components. The present work was performed to investigate the effects of Korean mistletoe lectin (Viscum album L. coloratum agglutinin, VCA) on proliferation and apoptosis of human hepatoma cells as well as the underlying mechamisms for these effects. We showed that VCA induced apoptosis in both SK-Hep-1 (p53-positive) and Hep 3B (p53-negative) cells through p53- and p21-independent pathways. VCA induced apoptosis by down-regulation of Bcl-2 and by up-regulation of Bax functioning upstream of caspase-3 in both cell lines. In addition, we observed down-regulation of telomerase activity in both VCA-treated cells. Our results provide direct evidence of the anti-tumor potential of this biological response which comes from inhibition of telomerase and consequent inducing apoptosis. VCA-induced apoptosis is regulated by mitochondrial controlled pathway independently of p53. These findings are important for the therapy with preparation of mistletoe because they show that telomerase-dependent mechanism can be targeted by VCA in human hepatocarcinoma. Taken together, our results suggest that the VCA, considered as a telomerase-inhibitor, can be envisaged as a candidate for enhancing sensitivity of conventional anticancer drugs.