Apoptotic mechanism of mistletoe (Viscum album) extract used in the treatment of cancer: Review


Cetin E. S. , ÖZÇELİK N.

TURKIYE KLINIKLERI TIP BILIMLERI DERGISI, cilt.27, sa.4, ss.533-539, 2007 (SCI İndekslerine Giren Dergi) identifier identifier

  • Cilt numarası: 27 Konu: 4
  • Basım Tarihi: 2007
  • Dergi Adı: TURKIYE KLINIKLERI TIP BILIMLERI DERGISI
  • Sayfa Sayıları: ss.533-539

Özet

Extracts of mistletoe (Viscum album) have been widely used as adjuvant chemoterapy in human cancer for many years. Their therapeutically active molecules are lectin components comprising lectin-I, lectin-II, and lectin-III. Incubation of different cell lines with lectins results in cell death associated with typical apoptotic alterations such as cell shrinkage, chromatin condensation, and internucleosomal DNA cleavage. Recent studies show that apoptosis is essentially controlled by a family of conserved proteases, called caspases, that are currently considered the central executioners of many apoptotic pathways. In mammalian cells, at least 12 different caspase members exist; they are initiator caspases (-8, -9, -10) and effector caspases (-3, -6, -7). Effector caspases cleave and inactivate DNA repair enzyme poly ADPribose polymerase (PARP), regulators of the cell cycle such as retinoblastoma protein and MDM-2, and structural proteins of the nucleus and cytoskeleton such as lamins, Gas2, gelsolin, and fodrin, survival proteins such as protein kinase C-delta (PKC-delta) and then cause cell death. The destructive mechanism of mistletoe lectins on tumor cells are mediated by the activation of c-JUN N-terminal kinase (JNK). Mistletoe lectin-II induces ladder pattern DNA fragmentation and activation of caspase -3, -8, and -9 of human myeloleukemic U937 cells, in a time- and dose-dependent manner. Consistent with catalytic activation of protease, both PARP and PKC-delta are also cleaved in mistletoe lectin-II-treated U937 cells. However, little is known about the mechanism of apoptosis induced by mistletoe lectin, even though there is convincing evidence that lectin-mediated anticancer properties are due to an activation of apoptotic processes.