crocin and Leukemia

Saffron (Crocus sativus L.), and its main constituents, crocin, and crocetin have shown promising effects as an antileukemic agent in animal models and cell culture systems. Saffron retards the growth of cancer cells via inhibiting nucleic acid synthesis and enhancing antioxidative system. It can induce apoptosis and chemosensitivity via inhibiting multidrug resistance proteins. Saffron also induces differentiation pathways via inhibiting promyelocytic leukemia/retinoic acid receptor-α, histone deacetylase1, and tyrosyl DNA phosphodiesterase-1 as well. The present review highlights the most recent findings on the antileukemic effects of saffron and its underlying molecular targets. The emerging evidence suggests that saffron has a selective toxicity effect against leukemic cells while is safe for the normal cells.

Topics: Animals; Antineoplastic Agents; Carotenoids; Cell Line, Tumor; Cell Proliferation; Crocus; Humans; Leukemia; Molecular Targeted Therapy; Plant Extracts; Randomized Controlled Trials as Topic; Xenograft Model Antitumor Assays

Among various naturally occurring compounds which have been extracted from Crocus sativus, crocin has shown different pharmacological effects i.e. neuroprotection and anti-tumor activity.. Here, crocin effects on human T-cell leukemia cell line, MOLT-4, were evaluated. In this study, we examined the effects of 24 and 48 h of crocin treatment (50, 250 and 500 µM) on the viability of MOLT-4 cell line. Moreover, probable apoptotic/necrotic outcomes, reactive oxygen species (ROS) production variations along with crocin treatment consequences on DNA, were investigated.. Results from MTT assay demonstrated that 48-h crocin treatment at 500 µM, significantly reduced cell viability (p<0.01). DNA fragmentation was recorded to be significantly increased at higher doses of crocin following 24 and 48 h (p<0.01). According to our results, while apoptosis was detected at all concentrations, necrosis detected at the highest dose, only. In comparison with control, ROS production was reduced at 50 and 250 µM.. In accordance with previous reports, crocin exhibited mild cytotoxic effects on a leukemia cell line which might be mediated through the increase of DNA fragmentation.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Carotenoids; Cell Line, Tumor; Cell Survival; Crocus; DNA Fragmentation; Humans; Leukemia; Necrosis; Phytotherapy; Plant Extracts; Reactive Oxygen Species

This study was purposed to investigate the effect of crocin on the proliferation in vitro and immune function of dendritic cells (DC) derived from the bone marrow of children with acute leukemia. The mononuclear cells were isolated from bone marrow of leukemia children by Ficoll-Hypaque. The experiment was divided into six groups: blank control group (A), crocin 1.25 mg/ml group (B), cytokines (rhGM-CSF 75 ng/ml+rhIL-4 75 ng/ml+rhTNF-α 50 ng/ml) group (C), cytokines+crocin 0.3125, 1.25 or 5.0 mg/ml groups (D, E, F). The numbers of DC were counted and the phenotypes of DC were determined by flow cytometry on the ninth day of culture. The DC of different groups were mixed with T cells just separated from peripheral blood of another children with acute lymphoblastic leukemia, and cultured with rhIL-2 200 U/ml for 5 d. The function of DC was detected by mixed lymphocyte reaction (MLR). The results indicated that the test groups and control group all obtained a certain amount of typical DC, but the DC numbers in test groups were all higher than those in control group (P < 0.01). Cultured for 9 days, the rates of CD1a(+), CD83(+), and HLA-DR(+) in group C, D, E, F were higher than group A (P < 0.01). There was no statistically significant difference between A and B groups (P > 0.05). MLR showed that with the increasing of DC, the stimulation index of T cells in group A and B was not rising (P > 0.05); the stimulated index of T cells in group C and E was significantly rising, there was statistically significant difference between them (P < 0.01). When the number of stimulated cells was the same, the stimulation index of T cell in group E was the highest (P < 0.01). It is concluded that the capability of DC proliferation promoted by crocin alone is lower than that of its combination with rhGM-CSF, rhIL-4 and rhTNF-α, but the crocin can synergically promote the maturity of DC cooperating with rhGM-CSF, rhIL-4 and rhTNF-α. The DC induced by crocin can particularly enhance the proliferation of T cells.

Topics: Bone Marrow Cells; Carotenoids; Cell Proliferation; Child; Dendritic Cells; Humans; Leukemia; Lymphocyte Culture Test, Mixed; T-Lymphocytes; Tumor Cells, Cultured

This study was to investigate the proliferative inhibition and apoptosis of human leukemia HL-60 cells induced by crocin and their possible mechanisms. The cell viability was tested by cell counting. The morphology of HL-60 cells was observed by fluorescence microscopy. The MTT assay was used to evaluate the inhibitory effect of crocin on the growth of HL-60 cells. Flow cytometry was used to measure the cell cycle. RT-PCR was used to detect bcl-2 and bax expression. The results indicated that the growth of HL-60 cells was inhibited remarkably in the dose and time dependent way. When the crocin concentration was higher than 5 mg/ml, the percentage of apoptotic HL-60 cells was not increased, on the contrary this percentage decreased, the cells manifested necrosis. Flow cytometry profiles revealed that cells were blocked in G₀/G₁ phase, the cell proliferation was inhibited obviously at 5 mg/ml. RT-PCR detection revealed that the expression of bcl-2 was down-regulated strikingly and bax was up-regulated. It is concluded that the crocin can inhibit the proliferation of HL-60 cells effectively, and block cells in G₀/G₁ phase. The mechanisms by which crocin induced apoptosis in HL-60 cells may be related to the inhibition of bcl-2 and activation of bax.

Topics: Apoptosis; bcl-2-Associated X Protein; Carotenoids; Cell Cycle; Cell Proliferation; Gene Expression Regulation, Leukemic; HL-60 Cells; Humans; Leukemia; Phytotherapy; Proto-Oncogene Proteins c-bcl-2