Interaction of vitamin D derivatives and granulocyte–macrophage colony-stimulating factor in leukaemic cell differentiation

James, SY; Ma, Williams; Kelsey, SM; Newland, A. C.; Colston, K. W.

doi:10.1038/sj.leu.2400676

Cited by 18 publications

(6 citation statements)

References 7 publications

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“…Consistent with previous reports, 33 GM-CSF alone showed a minor effect on HL-60 ( Figure 5a) and U937 (Figure 5b) differentiation, with maximal increase of NBT-positive cells (8-10%) at day 6. Interestingly, the percentage of NBT-positive cells in HL-60 cultured in the presence of both GM-CSF and SS was increased to 83% compared to 60% with SS alone (Figure 5a) or 90% with ATRA alone (Figure 4b).…”

Section: Ss-induced Differentiation Of Hl-60 and U937 Is Augmented Bysupporting

confidence: 80%

Effects of sodium stibogluconate on differentiation and proliferation of human myeloid leukemia cell lines in vitro

Pathak

2002

Leukemia

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PTPases are key signaling molecules and targets for developing novel therapeutics. We have studied the in vitro biological activity of PTPase inhibitor sodium stibogluconate (SS) on differentiation and proliferation of myeloid leukemia cell lines (NB4, HL-60 and U937). SS (250 g/ml, 6 days) induced 87% of NB4 cells to reduce nitroblue tetrazolium (NBT), in comparison to the 90% induced by ATRA (1 M, 6 days). SS treatment of NB4 cells resulted in an increase of CD11b expression and of a morphologically more mature population, coincident with growth arrest at S phase and increased cell death. The effect of SS on NB4 differentiation was irreversible and required continuous drug exposure. SS (400 g/ml, 6 days) induced 60% and 55% of NBT-positive cells in HL-60 and U937 cell lines, which were augmented in the presence of GM-CSF (25 ng/ml) to levels (85% and 81%, respectively) comparable to those induced by ATRA. SS induced increased tyrosine phosphorylation of cellular proteins in the AML cell lines and inactivated SHP-1 PTPase in NB4 cells, consistent with SS functioning as a PTPase inhibitor in the leukemia cells. These results provide the first evidence of an anti-leukemia activity of SS as a PTPase inhibitor.

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Section: Ss-induced Differentiation Of Hl-60 and U937 Is Augmented Bysupporting

confidence: 80%

Effects of sodium stibogluconate on differentiation and proliferation of human myeloid leukemia cell lines in vitro

Pathak

2002

Leukemia

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“…In the current study, induction of differentiation by lycopene was demonstrated by the development of the NADPH oxidase (as measured by NBT reduction), which represents one of the characteristic functions of mature monocytes and granulocytes, and by expression of CD14 antigen (30,43). The CD14 expression data suggest that lycopene can induce differentiation toward monocytes to some extent.…”

Section: Discussionmentioning

confidence: 90%

Lycopene and 1,25‐dihydroxyvitamin d₃cooperate in the inhibition of cell cycle progression and induction of differentiation in hl‐60 leukemic cells

Amir

Karas

Giat

et al. 1999

Nutrition and Cancer

196

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Lycopene, the major tomato carotenoid, has been found to inhibit proliferation of several types of cancer cells, including those of breast, lung, and endometrium. By extending the work to the HL-60 promyelocytic leukemia cell line, we aimed to evaluate some mechanistic aspects of this effect. Particularly, the possibility was examined that the antiproliferative action of the carotenoid is associated with induction of cell differentiation. Lycopene treatment resulted in a concentration-dependent reduction in HL-60 cell growth as measured by [3H]thymidine incorporation and cell counting. This effect was accompanied by inhibition of cell cycle progression in the G0/G1 phase as measured by flow cytometry. Lycopene alone induced cell differentiation as measured by phorbol ester-dependent reduction of nitro blue tetrazolium and expression of the cell surface antigen CD14. Results of several recent intervention studies with beta-carotene, which have revealed no beneficial effects of this carotenoid, suggest that a single dietary component cannot explain the anticancer effect of diets rich in vegetables and fruits. Thus another goal of our study was to examine whether lycopene has the ability to synergize with other natural anticancer compounds, such as 1,25-dihydroxyvitamin D3, which when used alone are therapeutically active only at high and toxic concentrations. The combination of low concentrations of lycopene with 1,25-dihydroxyvitamin D3 exhibited a synergistic effect on cell proliferation and differentiation and an additive effect on cell cycle progression. Such synergistic antiproliferative and differentiating effects of lycopene and other compounds found in the diet and in plasma may suggest the inclusion of the carotenoid in the diet as a cancer-preventive measure.

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“…In addition, the phagocytotic activity of the cells, induction of superoxide production, expression of glycoprotein IIb/IIa, and the expression of enzymes like non-specific esterase (NSE) are enhanced when the cells are induced to differentiate. These markers have all been shown to be significantly up-regulated in response to treatment of leukaemia cells by vitamin D compounds in vitro with EB 1089 being more potent than 1α,25(OH) 2 D 3 [53,70,[119][120][121][122][123]. In a study using human HL-60 leukemia cells, induction of cell differentiation in response to 1α,25(OH) 2 D 3 and EB 1089 was demonstrated to be accompanied by upregulation of the p21 WAF1/CIP1 as well as a marked decrease of telomerase activity [70].…”

Section: Differentiationmentioning

confidence: 98%

Seocalcitol (EB 1089) A Vitamin D Analogue of Anti-cancer Potential. Background, Design, Synthesis, Pre-clinical and Clinical Evaluation

Hansen¹,

Hamberg²,

Binderup³

et al. 2000

CPD

104

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It is well established that the metabolically active form of vitamin D, 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) plays a key role in the establishment and maintenance of the calcium metabolism in the body. In addition to this classic effect of 1alpha,25(OH)2D3, substantial evidence has emerged demonstrating that 1alpha,25(OH)2D3 is able to regulate cell growth and differentiation in a number of different cell types, including cancer cells. However, the clinical usefulness of 1alpha,25(OH)2D3 is limited by its tendency to cause hypercalcaemia. Much effort has therefore been directed to identifying new vitamin D analogues with potent cell regulatory effects, but with weaker effects on the calcium metabolism than those of 1alpha,25(OH)2D3. One of these new synthetic analogues is Seocalcitol (EB 1089). Despite being 50-200 times more potent than 1alpha,25(OH)2D3 with respect to regulation of cell growth and differentiation in vitro as well as in vivo, EB 1089 displays a reduced calcaemic activity in vivo compared to that of 1alpha, 25(OH)2D3. These characteristics make EB 1089 a potentially useful compound for the treatment of cancer. Recent clinical evaluation of EB 1089 has focused mainly on establishing a maximum tolerated dose in cancer patients. Early results confirm that the low calcaemic activity observed in animals can be reproduced in the clinic. Furthermore, EB 1089 has been shown to induce regression of tumours, especially in hepatocellular carcinoma where complete remission has been obtained. In conclusion, the development of EB 1089 as an anti-cancer drug holds promise. However, its final evaluation must await the completion of ongoing controlled clinical trials.

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Interaction of vitamin D derivatives and granulocyte–macrophage colony-stimulating factor in leukaemic cell differentiation

Abstract: It will be inevitable that not all cells will respond to differen- enhanced efficacy in the treatment of certain disorders.

Cited by 18 publications

References 7 publications

Effects of sodium stibogluconate on differentiation and proliferation of human myeloid leukemia cell lines in vitro

Effects of sodium stibogluconate on differentiation and proliferation of human myeloid leukemia cell lines in vitro

Lycopene and 1,25‐dihydroxyvitamin d₃cooperate in the inhibition of cell cycle progression and induction of differentiation in hl‐60 leukemic cells

Seocalcitol (EB 1089) A Vitamin D Analogue of Anti-cancer Potential. Background, Design, Synthesis, Pre-clinical and Clinical Evaluation

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Interaction of vitamin D derivatives and granulocyte–macrophage colony-stimulating factor in leukaemic cell differentiation

Abstract: It will be inevitable that not all cells will respond to differen- enhanced efficacy in the treatment of certain disorders.

Cited by 18 publications

References 7 publications

Effects of sodium stibogluconate on differentiation and proliferation of human myeloid leukemia cell lines in vitro

Effects of sodium stibogluconate on differentiation and proliferation of human myeloid leukemia cell lines in vitro

Lycopene and 1,25‐dihydroxyvitamin d3cooperate in the inhibition of cell cycle progression and induction of differentiation in hl‐60 leukemic cells

Seocalcitol (EB 1089) A Vitamin D Analogue of Anti-cancer Potential. Background, Design, Synthesis, Pre-clinical and Clinical Evaluation

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Product

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Lycopene and 1,25‐dihydroxyvitamin d₃cooperate in the inhibition of cell cycle progression and induction of differentiation in hl‐60 leukemic cells