Inhibition of Tumor Growth and Metastasis by Korean Mistletoe Lectin is Associated with Apoptosis and Antiangiogenesis

Abstract

The mistletoe lectins are major active components in the extract of European mistletoes that have been widely used in adjuvant chemotherapy of cancer. This study was performed to investigate the mechanism of anticancer and antimetastatic activity of the purified Korean mistletoe lectin (Viscum album L. coloratum agglutinin, VCA). C57BL6 mice inoculated with B16-BL6 melanoma cells and treated with VCA were assessed for survival and metastasis. The induction of apoptosis of B16-BL6 cells by VCA was investigated by morphological changes, DNA fragmentation characteristics, and cell cycle analysis. The antiangiogenic activity of VCA was also measured by the CAM (choriallantoic membrane) assay. Length of survival of mice was increased and lung metastasis was inhibited by VCA. Treatment of cells with VCA resulted in growth suppression, nuclear morphological changes, DNA fragmentation, and an increased fraction of cells in sub-G1 consistent with apoptosis. Antiangiogenesis of VCA was assessed by CAM assay, where vessel growth induced by fat emulsion was decreased. These results suggest that VCA inhibits tumor growth and metastasis by increasing apoptosis and inhibiting angiogenesis.

Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model

“…To analyse whether the European ML-I acts as an antiangiogenic agent, as has been discussed for Korean ML-I (Yoon et al, 1995;Park et al, 2001), we quantified the number of tumour-infiltrating vessels. However, no antiangiogenic effect of the European ML-I could be shown in our model.…”

“…In addition to its cytotoxic effect, ML-I might have further impact on tumour growth and metastases through its stimulation of the immune system, raising the number and the activity of NK cells, dendritic cells (DCs) and granulocytes (Hajto et al, 1997;Pryme et al, 2006). Furthermore, antiangiogenic effects have been described for the Korean ML-I (Park et al, 2001).…”

Potential Anti-Tumor and Anti-Inflammatory Activity of Six Mistletoe Plants in the Family Viscaceae Present in Western Ghats, India

“…V. album contains several active components such as mistletoe lectins [8] viscotoxins [9], alkaloids [10] and polysaccharides [11] which are reported to show anti-tumor properties by causing cell cycle delay or arrest and induction of apoptosis [12]. It inhibits tumor angiogenesis [13,14] and exert immune-potentiating activities that enhance the host defense system against tumors [15; 16]. Compounds of mistletoe origin are also been reported to show in vitro inhibitory potential on multidrug resistance protein (MDR1) [17].…”

Poblaciones linfocitarias, células dendríticas y perfil de citoquinas en ratones con melanoma tratados con Uncaria tomentosa

“…La dosis estandarizada para la inoculación subcutánea fue 5x10 4 células/100 uL de suspensión. Las células se inocularon en el flanco izquierdo de la región abdominal.…”

“…Las investigaciones con plantas medicinales tienen resultados alentadores. Park W-B et al evaluaron el efecto de las lectinas de Viscum album (muérdago) en ratones con melanoma, encontrando un efecto proapoptótico, antiangiogénico, antimetastásico e incrementador de la supervivencia (4) . Currier NL et al demostraron un aumento de células Natural killer (NK) en ratones con leucemia y tratados con Echinacea purpurea (Equinacea) (5) .…”