ATRA he Effects of Cytotoxicity, Differentiation and Apoptosis of Viscum Album Lectin Extract on HL60 Cells Individually and in Combination with ATRA

Acute promyelocytic Leukemia(APL) is a kind of acute leukemia characterized by a balanced t(15, 17) translocation and the accumulation of neoplastic promyelocytes which fails to develop into mature cells. In the recent years, chemotherapy, differentiation agents and apoptotic drugs have beed used in treatment of leukemia. Recently, plant extracts have been used for treatment of cancers in research and clinical application. The aim of the present research was to study cytotoxicity differentiation and apoptosis of viscum album lectin extract on HL60 cells individually or in combination with ATRA. Cytotoxic effect of extract on HL60 cells was studied by MTT colorometric assay and viability was monitored using cell counting and trypan blue. Differentiation induction of cells after treatment was examined by Geimsa staining, NBT test and evaluation of CD11b and CD14 markers flowcytometry. Apoptosis was also observed using Annexin and PI through flowcytometry. The data showed this extract was not cytotoxic in lower than 20µg/ml in 72hrs, but it had cytotoxic effect over this concentration in a dose and time-dependent manner. In concentrations of 30µg/ml, cell proliferation decreased with good viability revealing antiproliferative effects of this agent. However, differentiation induction effect was not observed with this agent. In proper dose(100µg/ml) in 24 hrs, little evidence of apoptosis was seen compared to dexamethasone(dexamethasone as a positive control). The combination of this agent with ATRA did not show any effect on differentiation of cells. However, ATRA preserved its effect of differentiation with higher cessation of proliferation. This extract had antiproliferation and cytotoxic effect on HL60 cells depending on concentration. However, effect on apoptosis was minimal. The combination of this extract with cytotoxic drugs and differentiation agents requires further investigation.