Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulators that play an important role in the differentiation and development of plants or invertebrates may also affect the differentiation of human leukaemia cells through a common signal transduction system, and might be clinically useful for treating acute myeloid leukaemia. Cotylenin A has been isolated as a plant growth regulator. We examined the effects of cotylenin A on the differentiation of several myelogenous leukaemia cells, and found that cotylenin A is a potent and novel inducer of the monocytic differentiation of human myeloid leukaemia cells. Cotylenin A induced the functional and morphological differentiation of myeloblastic and promyelocytic leukaemia cells, but did not effectively induce the differentiation of monocytoid leukaemia cells. Cotylenin A-induced differentiation was not affected by several inhibitors of signal transduction, suggesting that this inducer exhibits a unique mode of action.
 ...
PMID:Induction of the monocytic differentiation of myeloid leukaemia cells by cotylenin A, a plant growth regulator. 1126 75

Cotylenin A, which has a diterpenoid tricarbocyclic skeleton, has been isolated as a plant growth regulator, has been shown to affect several physiological processes of higher plants and have differentiation-inducing activity in several myeloid leukaemia cell lines. We examined the effect of cotylenin A on the differentiation of leukaemic cells that were freshly isolated from acute myeloid leukaemia (AML) patients in primary culture. Cotylenin A significantly stimulated both functional and morphological differentiation of leukaemia cells in 9 out of 12 cases. This differentiation-inducing activity was more potent than those of all-trans retinoic acid and 1alpha,25-dihydroxyvitamin D3 (VD3). Treatment with a combination of cotylenin A and VD3 was more effective than cotylenin A or VD3 alone at inducing the monocytic differentiation of AML cells.
 ...
PMID:Differentiation of human acute myeloid leukaemia cells in primary culture in response to cotylenin A, a plant growth regulator. 1156 68

Acute myeloid leukemia (AML) is characterized by the arrest of differentiation leading to the accumulation of immature cells. This maturation arrest can be reversed by certain agents. Although differentiation therapy for patients with acute promyelocytic leukemia (APL) using all-trans retinoic acid (ATRA) has been established, the clinical response of AML patients other than those with APL to ATRA is limited. We must consider novel therapeutic drugs against other forms of AML for the development of a differentiation therapy for leukemia. Regulators that play an important role in the differentiation and development of plants or invertebrates may also affect the differentiation of human leukemia cells through a common signal transduction system, and might be clinically useful for treating AML. Cotylenin A, a plant growth regulator, is a potent and novel inducer of the monocytic differentiation of human myeloid leukemia cell lines and leukemia cells freshly isolated from AML patients.
 ...
PMID:Cotylenin A--a plant growth regulator as a differentiation-inducing agent against myeloid leukemia. 1215 84

Although differentiation therapy for patients with acute promyelocytic leukemia (APL) using all-trans retinoic acid (ATRA) has now been established, acute myeloid leukemia (AML) patients with other than APL only show a limited clinical response to ATRA. We must consider novel therapeutic drugs against other AML to develop a differentiation therapy for leukemia. Regulators that play an important role in the differentiation and development of plants may also affect the differentiation of human leukemia cells through a common signal transduction system, and might be clinically useful for treating AML. Cytokinins are important purine derivatives that serve as hormones that control many processes in plants. Cytokinins such as kinetin, isopentenyladenine (IPA) and benzyladenine were very effective at inducing nitroblue tetrazolium (NBT) reduction and morphological changes in human myeloid leukemia cells into mature granulocytes. On the other hand, cytokinin ribosides such as kinetin riboside, isopentenyladenosine (IPAR) and benzyladenine riboside were the most potent for inhibiting growth and inducing apoptosis. When the cells were incubated with cytokinin ribosides in the presence of an O2- scavenger, antioxidant or caspase inhibitor, apoptosis was significantly reduced and differentiation was greatly enhanced. These results suggest that both cytokinins and cytokinin ribosides can induce the granulocytic differentiation of HL-60 cells, but cytokinin ribosides also induce apoptosis prior to differentiation. Cotylenin A has been isolated as a plant growth regulator exhibits cytokinin-like activity. Although it has a different structure than cytokinins, it also induces the differentiation of human myeloid leukemia cells. These results suggest that there is an association between the action of plant redifferentiation-inducing hormones and the mechanism of the differentiation of human leukemia cells.
 ...
PMID:Differentiation of human myeloid leukemia cells by plant redifferentiation-inducing hormones. 1268 24

Cotylenin A, a novel inducer of the differentiation of leukemia cells, and IFN-alpha synergistically inhibited the growth of and induced apoptosis in several human non-small cell lung carcinoma cell lines. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor DR5 were the early genes induced by the combination of cotylenin A and IFN alpha in lung carcinoma cells. Neutralizing antibody to TRAIL inhibited apoptosis, suggesting that cotylenin A and IFN alpha cooperatively induced apoptosis through the TRAIL signaling system. This combined treatment preferentially induced apoptosis in human lung cancer cells while sparing normal lung epithelial cells and significantly inhibited the growth of human lung cancer cells as xenografts without apparent adverse effects, suggesting that this combination may have therapeutic value in treating lung cancer.
 ...
PMID:Cotylenin A, a differentiation-inducing agent, and IFN-alpha cooperatively induce apoptosis and have an antitumor effect on human non-small cell lung carcinoma cells in nude mice. 1283 56

Cotylenin A has differentiation-inducing activity in human myeloid leukemia cell lines and leukemic cells that were freshly isolated from acute myeloid leukemia (AML) patients in primary culture. Injection of the human promyelocytic leukemia cell line NB4 into SCID mice resulted in the death of all mice due to leukemia. Administration of cotylenin A significantly prolonged the survival of mice inoculated with NB4 cells. In an in vivo analysis, cotylenin A induced the differentiation of leukemia cells in a retinoid-resistant leukemia model. Cotylenin A may be useful for differentiation therapy of retinoid-resistant leukemia.
 ...
PMID:Treatment of human promyelocytic leukemia in the SCID mouse model with cotylenin A, an inducer of myelomonocytic differentiation of leukemia cells. 1285 95

Cotylenin A, which has been isolated as a plant growth regulator, potently induces the differentiation of human myeloid leukemia cells. Treatment of HL-60 cells with a combination of transforming growth factor (TGF)-beta and 1alpha, 25-dihydroxyvitamin D(3) (VD3) resulted in increased differentiation compared to separate treatments, but TGF-beta did not affect the cotylenin A-induced differentiation of HL-60 cells. It is possible that the signal transduction pathway used by cotylenin A for inducing the differentiation of leukemia cells is the same as that used by TGF-beta. However, cotylenin A did not affect the expression of TGF superfamily or Smad genes in HL-60 cells. Treatment with neutralizing anti-TGF-beta antibody or an inhibitor of TGF-beta signaling did not inhibit cotylenin A-induced differentiation, although VD3-induced differentiation was significantly suppressed by these treatments. The subcellular distribution of Smad3 was also unaffected by cotylenin A. These results suggest that the cotylenin A-induced differentiation of leukemia cells is independent of the TGF-beta signaling system, although TGF-beta acts as an autocrine mediator of the growth arrest and differentiation of leukemia cells induced by VD3 and other inducers.
 ...
PMID:Cotylenin A-induced differentiation is independent of the transforming growth factor-beta signaling system in human myeloid leukemia HL-60 cells. 1669 May 33

A low concentration of differentiation inducers greatly enhances the in vitro and in vivo antiproliferative effects of interferon (IFN)alpha in several human cancer cells. Among the differentiation inducers tested, the sensitivity of cancer cells to IFNalpha was most strongly affected by cotylenin A. Cotylenin A, which is a novel fusicoccane diterpene glycoside with a complex sugar moiety, affected the differentiation of leukemia cells that were freshly isolated from acute myelogenous leukemia patients in primary culture. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor DR5 were early genes induced by the combination of cotylenin A and IFNalpha in carcinoma cells. Neutralizing antibody to TRAIL inhibited apoptosis, suggesting that cotylenin A and IFNalpha cooperatively induced apoptosis through the TRAIL signaling system. Combined treatment preferentially induced apoptosis in human lung cancer cells while sparing normal lung epithelial cells. In an analysis of various cancer cell lines, ovarian cancer cells were highly sensitive to combined treatment with cotylenin A and IFNalpha in terms of the inhibition of cell growth. This treatment was also effective toward ovarian cancer cells that were refractory to cisplatin, and significantly inhibited the growth of ovarian cancer cells as xenografts without apparent adverse effects. Ovarian cancer cells from patients were also sensitive to the combined treatment in primary cultures. Combined treatment with cotylenin A and IFNalpha may have therapeutic value in treating human cancers including ovarian cancer.
 ...
PMID:Therapeutic strategy using phenotypic modulation of cancer cells by differentiation-inducing agents. 1764 78

Lithocholic acid (LCA) acetate induced the differentiation of human leukemia cells. Treatment with a combination of LCA acetate and cotylenin A, an inducer of the differentiation of leukemia cells, was more effective than that with LCA acetate or cotylenin A alone at inducing monocytic differentiation. LCA acetate activated mitogen-activated protein kinase (MAPK) before inducing differentiation. Cotylenin A did not activate MAPK, suggesting that cotylenin A has a different mode of action. The cooperative effects of LCA acetate and cotylenin A on inducing differentiation were, at least partly, due to the enhancement of LCA acetate-induced MAPK activation by cotylenin A.
 ...
PMID:Induction of differentiation of myeloid leukemia cells in primary culture in response to lithocholic acid acetate, a bile acid derivative, and cooperative effects with another differentiation inducer, cotylenin A. 1824 98