Induction of differentiation and down-regulation of c-myb gene expression in ML-1 human myeloblastic leukemia cells by the clinically effective anti-leukemia agent meisoindigo

Liu, Xiao M.; Wang, Long G.; Li, Hong Y.; Ji, Xiu J.

doi:10.1016/0006-2952(96)00098-6

Cited by 42 publications

(27 citation statements)

References 12 publications

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“…The antitumor properties of some of these compounds have been studied with respect to apoptosis and cell cycle arrest. Indirubin and several of its analogues exhibit their anticancer activity through modulating CDKs, which will arrest cell cycle progression leading to cell death by apoptosis [17,18,19,20,22,23,25,26,27,28]. Multiple indirubin derivatives have been shown to arrest cell cycle at G0/G1 phase at low micromolar concentrations (up to 1 µM), while higher concentrations, ≥ 5 µM, inhibit cell cycle at G2/M phase [23].…”

Section: Discussionmentioning

confidence: 99%

“…Several of these compounds have been shown to inhibit CDKs and glycogen-synthase kinase (GSK-3β) and induce apoptosis in leukemic cells with varying degrees of potency [17,18,19,20,22,23,25,26,27,28]. In spite of extensive investigations on the mode of action of isoindigos in various malignancies, comprehensive study is yet to be done.…”

Section: Introductionmentioning

confidence: 99%

“…While indigo is mainly used as a textile dye, indirubin was identified as the active ingredient of a traditional Chinese recipe (Danggui Longhui Wan) used for treatment of chronic myelogenous leukemia (CML) [16,17]. Indirubin exerts its antileukemic effect through multi-signaling pathways including inhibition of DNA biosynthesis and assembly of microtubules, arresting cell cycle at G1 phase, interaction with the aryl hydrocarbon receptor (AhR) and down-regulation of c-myb gene expression [17,18,19,20,21]. The impairment of cell cycle progression in CML cells by Indirubin is mediated by the ability of the compound to compete with ATP for binding to the catalytic subunit of CDKs, leading to inhibition of these enzymes [22,23].…”

Section: Introductionmentioning

confidence: 99%

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The Anticancer Activity of the Substituted Pyridone-Annelated Isoindigo (5'-Cl) Involves G0/G1 Cell Cycle Arrest and Inactivation of CDKs in the Promyelocytic Leukemia Cell Line HL-60

Saleh

Aljada

El‐Abadelah

et al. 2015

Cell Physiol Biochem

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Background/Aims:The antileukemic potential of isoindigos make them desired candidates for understanding their mechanism of action. We have recently synthesized a novel group of pyridone-annelated isoindigos and identified the derivative 5'-Cl that is cytotoxic to various cancer cell lines. In the present study, we analyzed the effect of this compound on cell cycle of the promyelocytic leukemia cell line HL-60. Methods:HL-60 cells were treated with 5'-Cl and its effect on cell cycle stages were determined by flow cytometry. Expression of cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) were determined by Western blotting, and activation of CDKs was studied using kinase assays. Results:5'-Cl remarkably arrested cell cycle in HL-60 cells at the G0/G1 phase in a dose and time-dependent manner. Furthermore, 5'-Cl treatment significantly inhibited expression of D-cyclins, CDK2 and CDK4 and suppressed phosphorylation of the retinoblastoma protein Rb, whereas it increased the level of CKI p21. Molecular modelling experiments show that 5'-Cl may compete with ATP for binding to the catalytic subunit of CDK2 and CDK4 that could lead to inhibition of these enzymes. Indeed, 5'-Cl inhibited the kinase activity of CDK2 and CDK4 both in cell free systems and in treated cells. 5'-Cl also inhibited cell cycle progression in several other tumor cell lines. Conclusion:We demonstrate the potent inhibitory effects of 5'-Cl on HL-60 cells could be mediated by arresting cells in the G0/G1 phase.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Anticancer Activity of the Substituted Pyridone-Annelated Isoindigo (5'-Cl) Involves G0/G1 Cell Cycle Arrest and Inactivation of CDKs in the Promyelocytic Leukemia Cell Line HL-60

Saleh

Aljada

El‐Abadelah

et al. 2015

Cell Physiol Biochem

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“…Another indirubin derivative, meisoindigo, strongly inhibits DNA biosynthesis and microtubule assembly in tumor cells (15). Meisoindigo also induces the leukemic cell differentiation by decreasing the c-myb expression (16).…”

mentioning

confidence: 99%

Antitumor Activity of Novel Indirubin Derivatives in Rat Tumor Model

Kim

et al. 2007

Clinical Cancer Research

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Purpose: The novel indirubin derivatives 5 ¶-nitro-indirubinoxime, 5 ¶-fluoro-indirubinoxime, and 5 ¶-trimethylacetamino-indirubinoxime were designed and tested for antitumor activity both in vitro and in vivo using rat tumor model. Experimental Design: Three-week-old male Sprague-Dawley rats were inoculated s.c. on the left flank with 10 7 RK3E-ras rat kidney epithelial cells harboring k-ras gene. Alternatively, 5 Â 10 6 RK3E-ras cells were injected into the oral mucosa. Indirubin derivative treatment began on the 3rd or 6th day after oral or s.c. cell injection, respectively. Indirubin derivatives were directly injected into the tumor every other day for a total of five times. Animals were monitored daily and tumor volume was measured by caliper.Results: Indirubin derivatives showed potent antiproliferative activity on various human cancer cells and oncogenic RK3E-ras rat kidney cells, with IC 50 ranging from 1 to 12 Amol/L. Treatment with indirubin derivatives induced the activation of caspase-7 followed by apoptosis in RK3E-ras cells. Indirubin derivatives showed strong antitumor activity in rat solid and oral tumor models. Direct injection of indirubin derivatives every other day for 10 days induced significant inhibition of tumor growth in Sprague-Dawley rats bearing RK3E-ras-induced tumors. Histologically, treatment with indirubin derivatives caused significant inhibition of tumor formation with increased apoptosis and decreased tumor cell proliferation. Conclusions: Our data showed that novel indirubin derivatives 5 ¶-nitro-indirubinoxime, 5 ¶-fluoro-indirubinoxime, and 5 ¶-trimethylacetamino-indirubinoxime effectively arrested the tumor growth by inhibiting cell proliferation and inducing apoptosis.These findings provide the potential value of indirubin derivatives as novel candidates for antitumor agents.

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“…Isatins are widely employed in the synthesis of various biologically active compounds, such as functionalized indirubins [25] or regioisomeric isoindigos [26,27], exemplified by meisoindigo (Fig. 1); the latter compound is used in China for the treatment of chronic myelocytic leukemia [28].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 6-Ethyl-1,2,9-trioxopyrrolo[3,2-f ]quinoline-8-carboxylic Acid

Voelter¹

2013

Zeitschrift Für Naturforschung B

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Interaction of 6-amino-1-ethyl-4-oxoquinoline-3-carboxylic ester (7) with chloral hydrate and hydroxylamine hydrochloride gave the corresponding isonitroso-acetamido derivative 8 which, upon treatment with concentrated sulfuric acid, was converted regioselectively into 1,2,9-trioxopyrrolo[3,2-f ]quinoline-8-carboxylic acid (3). This novel tricyclic system was isolated in good yield as a stable hydrate 3H. Structural assignments of the new compounds are based on microanalytical and spectral (MS and NMR) data.

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Induction of differentiation and down-regulation of c-myb gene expression in ML-1 human myeloblastic leukemia cells by the clinically effective anti-leukemia agent meisoindigo

Cited by 42 publications

References 12 publications

The Anticancer Activity of the Substituted Pyridone-Annelated Isoindigo (5'-Cl) Involves G0/G1 Cell Cycle Arrest and Inactivation of CDKs in the Promyelocytic Leukemia Cell Line HL-60

The Anticancer Activity of the Substituted Pyridone-Annelated Isoindigo (5'-Cl) Involves G0/G1 Cell Cycle Arrest and Inactivation of CDKs in the Promyelocytic Leukemia Cell Line HL-60

Antitumor Activity of Novel Indirubin Derivatives in Rat Tumor Model

Synthesis of 6-Ethyl-1,2,9-trioxopyrrolo[3,2-f ]quinoline-8-carboxylic Acid

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