Doxorubicin-CdS Nanoparticles: A Potential Anticancer Agent for Enhancing the Drug Uptake of Cancer Cells

2007 ◽  
Vol 7 (2) ◽  
pp. 435-439
Author(s):  
Jingyuan Li ◽  
Chunhui Wu ◽  
Yongyuan Dai ◽  
Renyun Zhang ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drug ◽  
K562 Cells ◽  
Biologically Active ◽  
Drug Uptake ◽  
Leukemia Cells ◽  
Target System ◽  
Cds Nanoparticles ◽  
Human Leukemia ◽  
Novel Strategy

A novel strategy of enhancing the drug uptake by cancer cells through the combination of anticancer drug doxorubicin with cadium sulfide (CdS) nanoparticles has been explored by using confocal fluorescence scanning microscopy as well as electrochemical studies, which demonstrates that CdS nanoparticles can readily conjugate with doxorubicin on the targeted cancer cells and facilitate the uptake of drug molecules in the human leukemia K562 cells. Besides, our observations also indicate that the aggregation of the leukemia cells occured when CdS nanoparticles were introduced into the relative target system together with doxorubicin, suggesting that the specific association of CdS nanoparticles with biologically active molecules on the surface of leukemia K562 cells may change some biorecognition or signal transfer pathway among cancer cells. It is suggested that the competitive binding of CdS nanoparticles with accompanying anticancer drug to the membrane of leukemia K562 cells could efficiently prevent the drug release by the drug resistant leukemia cells and thus inhibit the relative multidrug resistance (MDR) of targeted cancer cells.

Doxorubicin-CdS Nanoparticles: A Potential Anticancer Agent for Enhancing the Drug Uptake of Cancer Cells

2007 ◽  
Vol 7 (2) ◽  
pp. 435-439 ◽  
Author(s):  
Jingyuan Li ◽  
Chunhui Wu ◽  
Yongyuan Dai ◽  
Renyun Zhang ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drug ◽  
K562 Cells ◽  
Biologically Active ◽  
Drug Uptake ◽  
Leukemia Cells ◽  
Target System ◽  
Cds Nanoparticles ◽  
Human Leukemia ◽  
Novel Strategy

A novel strategy of enhancing the drug uptake by cancer cells through the combination of anticancer drug doxorubicin with cadium sulfide (CdS) nanoparticles has been explored by using confocal fluorescence scanning microscopy as well as electrochemical studies, which demonstrates that CdS nanoparticles can readily conjugate with doxorubicin on the targeted cancer cells and facilitate the uptake of drug molecules in the human leukemia K562 cells. Besides, our observations also indicate that the aggregation of the leukemia cells occured when CdS nanoparticles were introduced into the relative target system together with doxorubicin, suggesting that the specific association of CdS nanoparticles with biologically active molecules on the surface of leukemia K562 cells may change some biorecognition or signal transfer pathway among cancer cells. It is suggested that the competitive binding of CdS nanoparticles with accompanying anticancer drug to the membrane of leukemia K562 cells could efficiently prevent the drug release by the drug resistant leukemia cells and thus inhibit the relative multidrug resistance (MDR) of targeted cancer cells.

scholarly journals Potent Cytotoxicity of Novel L-Shaped Ortho-Quinone Analogs through Inducing Apoptosis

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4138
Author(s):  
Sheng-You Li ◽  
Ze-Kun Sun ◽  
Xue-Yi Zeng ◽  
Yue Zhang ◽  
Meng-Ling Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Furan Ring ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Prostate Cancer Cells ◽  
One Pot ◽  
Synthetic Strategy ◽  
Induced Apoptosis

Twenty-seven L-shaped ortho-quinone analogs were designed and synthesized using a one pot double-radical synthetic strategy followed by removing methyl at C-3 of the furan ring and introducing a diverse side chain at C-2 of the furan ring. The synthetic derivatives were investigated for their cytotoxicity activities against human leukemia cells K562, prostate cancer cells PC3, and melanoma cells WM9. Compounds TB1, TB3, TB4, TB6, TC1, TC3, TC5, TC9, TC11, TC12, TC14, TC15, TC16, and TC17 exhibited a better broad-spectrum cytotoxicity on three cancer cells. TB7 and TC7 selectively displayed potent inhibitory activities on leukemia cells K562 and prostate cancer cells PC3, respectively. Further studies indicated that TB3, TC1, TC3, TC7, and TC17 could significantly induce the apoptosis of PC3 cells. TC1 and TC17 significantly induced apoptosis of K562 cells. TC1, TC11, and TC14 induced significant apoptosis of WM9 cells. The structure-activity relationships evaluation showed that removing methyl at C-3 of the furan ring and introducing diverse side chains at C-2 of the furan ring is an effective strategy for improving the anticancer activity of L-shaped ortho-quinone analogs.

scholarly journals Sulforaphane Modulates AQP8-Linked Redox Signalling in Leukemia Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Cecilia Prata ◽  
Carlotta Facchini ◽  
Emanuela Leoncini ◽  
Monia Lenzi ◽  
Tullia Maraldi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Cell Signalling ◽  
Cell Types ◽  
Biologically Active ◽  
Leukemia Cells ◽  
Cruciferous Vegetables ◽  
Human Leukemia ◽  
Acute Myeloid

Sulforaphane, a biologically active isothiocyanate compound extracted from cruciferous vegetables, has been shown to exert cytotoxic effects on many human cancer cells, including leukemia. However, the exact molecular mechanisms behind the action of sulforaphane in hematological malignancies are still unclear. Like other cancer cells, leukemia cells produce high level of reactive oxygen species; in particular, hydrogen peroxide derived from Nox family is involved in various redox signal transduction pathways, promoting cell proliferation and survival. Recent evidence show that many tumour cell types express elevated level of aquaporin isoforms, and we previously demonstrated that aquaporin-8 acts as H2O2 transport facilitator across the plasma membrane of B1647 cells, a model of acute myeloid human leukemia. Thus, the control of AQP8-mediated H2O2 transport could be a novel strategy to regulate cell signalling and survival. To this purpose, we evaluated whether sulforaphane could somehow affect aquaporin-8-mediated H2O2 transport and/or Nox-mediated H2O2 production in B1647 cell line. Results indicated that sulforaphane inhibited both aquaporin-8 and Nox2 expression, thus decreasing B1647 cells viability. Moreover, the data obtained by coimmunoprecipitation technique demonstrated that these two proteins are linked to each other; thus, sulforaphane has an important role in modulating the downstream events triggered by the axis Nox2-aquaporin-8. Cell treatment with sulforaphane also reduced the expression of peroxiredoxin-1, which is increased in almost all acute myeloid leukemia subtypes. Interestingly, sulforaphane concentrations able to trigger these effects are achievable by dietary intake of cruciferous vegetables, confirming the importance of the beneficial effect of a diet rich in bioactive compounds.

scholarly journals Intrinsic growth heterogeneity of mouse leukemia cells underlies differential susceptibility to a growth-inhibiting anticancer drug

2020 ◽  
Author(s):  
Akihisa Seita ◽  
Hidenori Nakaoka ◽  
Reiko Okura ◽  
Yuichi Wakamoto
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Differential Susceptibility ◽  
Leukemia Cells ◽  
Continuous Exposure ◽  
Phenotypic Differences ◽  
Cell Lineages ◽  
Slow Cycling

AbstractCancer cell populations consist of phenotypically heterogeneous cells. Growing evidence suggests that pre-existing phenotypic differences among cancer cells correlate with differential susceptibility to anticancer drugs and eventually lead to a relapse. Such phenotypic differences can arise not only externally driven by the environmental heterogeneity around individual cells but also internally by the intrinsic fluctuation of cells. However, the quantitative characteristics of intrinsic phenotypic heterogeneity emerging even under constant environments and their relevance to drug susceptibility remain elusive. Here we employed a microfluidic device, mammalian mother machine, for studying the intrinsic heterogeneity of growth dynamics of mouse lymphocytic leukemia cells (L1210) across tens of generations. The generation time of this cancer cell line had a distribution with a long tail and a heritability across generations. We determined that a minority of cell lineages exist in a slow-cycling state for multiple generations. These slow-cycling cell lineages had a higher chance of survival than the fast-cycling lineages under continuous exposure to the anticancer drug Mitomycin C. This result suggests that heritable heterogeneity in cancer cells’ growth in a population influences their susceptibility to anticancer drugs.

Decreased Proliferation of Myeloid Leukemia Cells through Down-Regulating LYL1 Expression with Small Interference RNA.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4158-4158 ◽  
Author(s):  
Yuesheng Meng ◽  
Wei Liu ◽  
Xiaoxia Ma ◽  
Xiuqin Meng ◽  
Gongwen Ai ◽  
...  
Keyword(s):  
Growth Rates ◽  
Myeloid Leukemia ◽  
K562 Cells ◽  
Plating Efficiency ◽  
Leukemia Cell Line ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Small Interference Rna ◽  
Expression Levels ◽  
Interference Rna

Abstract Ectopic expression of the basic helix-loop-helix transcription factor LYL1 has been implicated in T-cell acute lymphoblastic leukemia (T-ALL). It has also been found to be over-expressed in cells of acute myeloid leukemia (AML). Myeloid leukemia cells over-expressing LYL1 cDNA had accelerated growth rates, increased plating efficiency and a blockade of differentiation. To further investigate its role in the pathogenesis of leukemia, we used small interference RNA (siRNA) to silence the expression of LYL1 in human leukemia cell line K562, which expresses a moderate level of endogenous LYL1 protein. Three LYL1-specific RNA oligos, the Stealth Select RNAi HSS142834, HSS142835, and HSS142836, purchased from Invitrogen, were introduced into K562 cells by using Invitrogen transfection reagent Lipofectamine RNAiMAX. Two successive transfections at day 1 and day 2 were made according to manufacturer’s manual. Expression levels of LYL1 in LYL1 siRNA transfected cells and control cells (transfected with the Stealth RNAi Negative Controls) were determined with fluorescence real-time quantitative polymerase chain reaction assay. Our result showed that the application of any single RNAi oligo achieved observable inhibition of LYL1 expression levels (30–40%) while a combination of the three RNAi oligos remarkable inhibition (70.4%). The growth rates of K562 cells were not affected by any single RNAi oligo. However, a combination of three RNAi oligos did induce noticeable growth inhibition of cells. Plating efficiency assay showed that the clonogenic recovery rate of K562 cells treated with a combination of thee RNAi oligos was inhibited by 32.5% (P<0.05). The reduced growth rate and clonogenicity of cells was supposed to be secondary to the repressed expression of LYL1 because all other factors were controlled in our experiments. Further experiments are underway to define the changes of other genes in the LYL1-suppressed cells. We also tested the effect of specific siRNA on the expression of LYL1 and clonogenecity of leukemia cells in patient samples. Mononuclear cells separated from nine newly-diagnosed AML patients whose cells expressed comparatively higher levels of LYL1 were transfected with a combination of three LYL1 specific siRNA oligos for twice. We found that the siRNA oligos suppressed the expression of LYL1 in leukemia cells in most of the patients (7/9, decreased by 2 times or more) when compared with controls. Remarkably, the clonogenicity of AML cells in 3 patients was also inhibited by siRNA (P<0.05). In conclusion, the specific siRNA was effective to downregulate the expression of LYL1 in myeloid leukemia cells. It was also effective to affect cell proliferation in some cases. The data demonstrates that LYL1 plays a role for the malignant genotypes of leukemia cells and suggests that the RNA interference therapy targeting specific oncogenes might be clinically useful in the management of hematological malignancies.

Butyrate-induced erythroid differentiation of human K562 leukemia cells involves inhibition of ERK and activation of p38 MAP kinase pathways

Blood ◽  
2000 ◽  
Vol 95 (7) ◽  
pp. 2391-2396 ◽  
Author(s):  
Olaf Witt ◽  
Katrin Sand ◽  
Arnulf Pekrun
Keyword(s):  
Signal Transduction ◽  
Map Kinase ◽  
K562 Cells ◽  
Erythroid Differentiation ◽  
P38 Map Kinase ◽  
Leukemia Cells ◽  
Common Mechanism ◽  
Signal Transduction Pathways ◽  
Human Leukemia ◽  
Mitogen Activated Protein

Butyrate induces cytodifferentiation in many tumor cells of different origin, suggesting that an as yet unidentified common mechanism inherent to malignant cells is the target of butyrate action. This study determined the role of different mitogen-activated protein (MAP) kinase signal transduction pathways in butyrate-induced erythroid differentiation of K562 human leukemia cells. Using a panel of anti-ERK, JNK, and p38 phosphospecific antibodies, the study showed that phosphorylation of ERK and JNK is decreased following treatment of cells with butyrate, whereas phosphorylation of p38 is increased. In contrast, a K562 subline defective in butyrate-mediated induction of erythroid differentiation did not reveal these changes in phosphorylation patterns. Inhibition of ERK activity by UO126 induces erythroid differentiation and acts synergistically with butyrate on hemoglobin synthesis and inhibition of cell proliferation, whereas inhibition of p38 activity by SB203580 completely abolished induction of hemoglobin expression by butyrate. Taken together, our data suggest a model in which butyrate induces erythroid differentiation of K562 cells by inhibition of ERK and activation of p38 signal transduction pathways.

scholarly journals Apoptosis induced by erythroid differentiation of human leukemia cell lines is inhibited by Bcl-XL

Blood ◽  
1996 ◽  
Vol 87 (9) ◽  
pp. 3837-3843 ◽  
Author(s):  
A Benito ◽  
M Silva ◽  
D Grillot ◽  
G Nunez ◽  
JL Fernandez-Luna
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Leukemia Cell ◽  
K562 Cells ◽  
Erythroid Differentiation ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Human Leukemia Cells ◽  
Leukemia Cell Lines ◽  
Wide Range

The induction of tumor cell differentiation represents an attractive strategy for the treatment of a wide range of malignancies. Differentiation of HL-60 promyelocytic leukemia cells towards neutrophils or monocytes has been shown to induce apoptotic cell death, which is inhibited by bcl-2 over-expression. However, the role of the bcl-2 gene family during erythroid differentiation of human leukemia cells remains unknown. We found that human erythroleukemia (HEL) and K562, two leukemia cell lines that undergo erythroid differentiation do not express Bcl-2, but express Bcl-XL, a related protein that functions as an inhibitor of apoptosis. Differentiation of HEL or K562 cells with inducers of erythroid differentiation (hemin, retinoic acid, or transforming growth factor-beta) was accompanied by progressive cell death and degradation of genomic DNA into oligonucleosomal fragments. The loss of cellular viability was associated with downregulation of bcl-xL mRNA and protein. In contrast, the levels of Bax, another Bcl-2 family member implicated in apoptosis remained unaltered. Constitutive expression of Bcl-XL by gene transfer inhibited apoptosis triggered by erythroid differentiation of HEL K562 cells. Yet, Bcl-XL did not alter the expression of epsilon-globin, which is induced during erythoid differentiation of HEL and K562 cells, arguing that apoptosis and differentiation can be uncoupled by Bcl-XL. These results indicate that Bcl-XL acts as an antiapoptosis protein in leukemia cells that undergo erythroid differentiation and that downregulation of bcl-x is a component of the apoptotic response that is coupled to differentiation in human leukemia cells.

The Effects of Site-Directed Mutation of SHIP Gene On the Regulating Mechanisms of PI3K/Akt Signal Pathway in Human Leukemia Cell Line K562.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5050-5050
Author(s):  
Jianmin Luo ◽  
Lin Yang ◽  
Xiaojun Liu ◽  
Shupeng Wen ◽  
Jingyu Zhang
Keyword(s):  
High Pressure ◽  
K562 Cells ◽  
Signal Pathway ◽  
Negative Regulator ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Wild Type ◽  
Directed Mutation ◽  
Group A ◽  
Group B

Abstract Abstract 5050 Introduction SHIP is an SH2 domain containing inositol-5-phosphatasse that appears to be a negative regulator of hematopoiesis. Our previous researching works have first reported that SHIP gene was genetically altered in leukemia patients and proved that mutation of SHIP gene was closely correlated with the increased phosphorylation of Akt and poor prognosis of AML patients; SHIP gene is a key regulative gene in the PI3K/Akt pathway, and transfection with wild type SHIP gene into K562 cell line can inhibit the proliferation of K562. Up to now, however, there are no any reports about what changes of the PI3K/Akt signal transduction regulation will happened if SHIP has site mutation in leukemia cells. The objectives of our study is to investigate the effects of site-directed mutation of SHIP on the expression level of the protein related to the PI3K/Akt signal pathway in leukemia cells, and to study the effects of site-directed mutation of SHIP on the key PIP3 activity related to the PI3K/Akt signal pathway in leukemia cells. Methods Based on the results of our previous studies, the absence of endogenous SHIP in K562 cells provided a useful systerm to study the role of SHIP in growth and apoptosis. The recombined lentivirus plasmids wtSHIP or muSHIPP28L were transfected stably into human leukemia cells K562. The cell proliferation, cell life cycle and cell apoptosis of K562 transfected with wid-type SHIP or muSHIPP28L were determined by MTT, fluorescent staining and flow cytometry. The expression level and difference of total Akt□Ap-Akt473 and p-Akt308 were reconfirmed by SDS-PAGE western blot. PI(3,4,5)P3 and PI(3,4)P2 was assayed by High pressure liquid chromatography. Results The decreased ability of proliferation and DNA synthesis, cell colony fomation ability and enhanced apoptosis rate were observed in K562 cells transfected with wild-type SHIP (Group A), but the same changes had not been observed in K562 cells transfected with muSHIPP28L (Group B) or empty vector (Group C). Wild-type SHIP can down-regulate phosphorylations of Akt308 and Akt473, but muSHIPP28L can't. High pressure liquid chromatography results showed that the PI3,4,5-P3 level was obviously decreased in Group A,no changes above indicate in Group B and Group C. The PI3,4P2 level in Group A was significantly higher than Group B and Group C. Conclusions The results confirmed SHIP as a negative regulator for cell proliferation in leukemia cells, and implied that it may function through its normal structure. Disclosures No relevant conflicts of interest to declare.

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