• Title, Summary, Keyword: human monocytic leukemia cells

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Cytotoxic Effect of Fruit of Prunus mandshurica on Human Monocytic Leukemia Cells

  • Chung, Ha-Sook
    • Preventive Nutrition and Food Science
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    • v.9 no.3
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    • pp.265-269
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    • 2004
  • Prunus mandshurica var. glabra Nakai (Rosaceae) is widely distributed in South Korea and bears a fruit with a bitter and astringent taste. An ethyl acetate-soluble extract of Prunus mandshurica was found to exhibit significant cytotoxicity against human leukemia cell lines. Bioassay-directed fractionation of this extract using an MTT(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) cell proliferation assay as a monitor led to the isolation of the bioactive compounds. Two compounds, 1 and 2 were subsequently found to mediate cytotoxicity against U937, human monocytic leukemia cells. The 50% growth inhibitory concentrations ($IC_{50}$/) of compounds 1 and 2 on U937 were 40 and 62 $\mu\textrm{g}$/mL, respectively.

Gelsolin Induces Promonocytic Leukemia Differentiation Accompanied by Upregulation of p21CIP1

  • Shirkoohi, Reza;Fujita, Hisakazu;Darmanin, Stephanie;Takimoto, Masato
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4827-4834
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    • 2012
  • Tumor suppressor genes have received much attention for their roles in the development of human malignancies. Gelsolin has been found to be down-regulated in several types of human cancers, including leukemias. It is, however, expressed in macrophages, which are the final differentiation derivatives for the monocytic myeloid lineage, implicating this protein in the differentiation process of such cells. In order to investigate the role of gelsolin in leukaemic cell differentiation, stable clones over-expressing ectopic gelsolin, and a control clone were established from U937 leukaemia cells. Unlike the control cells, both gelsolin-overexpressing clones displayed retarded growth, improved monocytic morphology, increased NADPH and NSE activities, and enhanced surface expression of the ${\beta}$-integrin receptor, CD11b, when compared with the parental U937 cells. Interestingly, RT-PCR and western blot analysis also revealed that gelsolin enhanced p21CIP1 mRNA and protein expression in the overexpressing clones. Moreover, transient transfection with siRNA silencing P21CIP1, but not the control siRNA, resulted in a reduction in monocytic differentiation, accompanied by an increase in proliferation. In conclusion, our work demonstrates that gelsolin, by itself, is capable of inducing monocytic differentiation in U937 leukaemia cells, most probably through p21CIP1 activation.

Compound K, Ginseng Saponin Metabolite, Induces Apoptosis in Human Monocytic Leukemia cells

  • Kang, Kyong-Ah;Kim, Dong-Hyun;Hyun, Jin-Won
    • Proceedings of the Korean Society of Applied Pharmacology
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    • pp.75-75
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    • 2003
  • We report upon the cytotoxic activity of the ginseng saponin metabolite, Compound K (20-O-D-glucopyranosyl-20(S)-protopanaxadiol, IH90l) on various human leukemia cell lines. Compound K had most effect on U937, a human monocytic leukemia cell line, which on treatment showed; a exposure of phosphatidylserine from the inner cell membrane to the outer cell membrane, the formation of apoptotic bodies and DNA fragmentation, - characteristics of apoptosis. Compound K induced apoptosis by up-regulating Bax, disrupting the mitochondria membrane potential, and by activating caspase 9 and caspase 3. Therefore, we suggest that Compound K inhibit U937 cell growth by inducing apoptosis through the up-regulation of Bax and caspase activation.

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The Pro-apoptotic Effects of S100A8 and S100A9 in Human Monocytic Leukemia Cells, THP-1

  • Kim, In-Sik;Lee, Ji-Sook
    • Biomedical Science Letters
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    • v.24 no.2
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    • pp.134-137
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    • 2018
  • S100A8 and S100A9 are involved in pathogenesis of cancer by induction or inhibition of cancer as well as inflammation. In this study, we investigated the association of S100A8 and S100A9 with pathogenesis of leukemia using human monocytic leukemia cells, THP-1. The expression of TLR4, which is a known receptor of S100A8 and S100A9, was examined by using flow cytometry and Western blotting. THP-1 cells have high surface and cytosol expression of TLR4. S100A8 and S100A9 suppressed the cell survival, and this suppression was found to be associated with apoptosis because they increased the number of apoptotic cells in a dose- and a time-dependent manners. However, S100A8 and S100A9 had no effect on the survival and apoptosis of monocytes isolated from the peripheral blood. We next examined the apoptotic effect of lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA), which are other ligands of TLR4, in THP-1 cells. Lipopolysaccharide had no effect on cell survival, but MPLA is effective on the cell apoptosis. These results suggest that S100A8 and S100A9 may regulate leukemia cell survival via TLR4, which is an essential receptor in the pro-apoptotic mechanism induced by S100A8 and S100A9. These findings may shed light on development of a possible therapeutic drug for leukemia treatment.

Inducing effect of helenalin on the differentiation of HL-60 leukemia cells

  • KIm, Seung-Hyun;Kim, Tae-Sung
    • Proceedings of the PSK Conference
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    • pp.166.3-166
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    • 2003
  • Helenalin, a cell-permeable pseudoguainolide sesquiterpene lactone, is a potent anti-inflammatory agent that inhibits $NF-{\kappa}B$ DNA binding activity by selectively alkylating the p65 subunit of $NF-{\kappa}B$. Transcription factors such as $NF-{\kappa}B$ provide powerful target of drugs to use in the treatment of cancer. Human promyelocytic leukemia HL-60 cells are differentiated into monocytic or granulocytic lineage when treated with 1,25-dihydroxyvitamin $D_3{\;}[1,25-(OH)_2D_3]$ or all-trans-retinoic acid (ATRA), respectively. (omitted)

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Inhibitory effect of Panax ginseng and Pleurotus osteratus complex on expression of cytokine genes induced by extract of Dermatophagoides pteronissinus in human monocytic THP-1 and EoL-1 cells

  • Park, Kyeong Hun;Lee, Eun Suk;Jin, Yong Ik;Myung, Kyung Sun;Park, Hong Woo;Park, Chun Geon;Kong, Won Sik;Kim, Young Ock
    • Journal of Mushroom
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    • v.14 no.4
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    • pp.155-161
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    • 2016
  • A recent study reported that Pleurotus ostreatus has the potential to be used as a ${\beta}-glucan-based$ cream for supportive complementary therapy of atopic dermatitis. KH054 is a new herbal prescription consisting of P. ostreatus and Panax ginseng. The effects of atopic dermatitis-induced materials on the expression of cytokine genes in human monocytes (THP-1, EoL- 1) have been examined. Some reports demonstrated that P. ginseng augments the activity of natural killer cells, which plays an important role in innate immunity against infection and tumor development. Monocyte chemotactic protein 1 (MCP-1), interleukin (IL)-6, and IL-8 have important roles in mediating the infiltration of various cells into the skin of atopic dermatitis and psoriasis. The present study investigated whether KH054 on induced IL-6, IL-8, and MCP-1 secretion by house dust mite (Dermatophagoides pteronissinus) in THP-1 (human acute monocytic leukemia) and EoL-1(Human eosinophilic leukemia) cell. D. pteronissinus functions in the pathogenesis of allergic diseases, including atopic dermatitis and asthma. The inhibitory effect of KH054 on the induction of IL-6, IL-8, and MCP-1 secretion by D. pteronissinus extract in THP-1 and EoL-1 cells was examined. KH054 potently suppressed the elevated production of IL-6 and IL-8 induced by D. pteronissinus treatment in THP-1 and EoL-1 cells. Based on the present results, KH054 may be useful for developing functional foods to treat atopic dermatitis.

Decursin from Angelica gigas Nakai Promotes Cytotoxicity and Induces Apoptosis in THP-1 cells, a Human Acute Monocytic Leukemia (당귀로부터 정제한 Decursin의 인간 급성 단핵구성 백혈병 세포(THP-1 cells)의 세포 독성 및 Apoptosis에 미치는 영향)

  • Kim, Nam-Seok;Jeong, Seung-Il;Kim, Jong-Seok;Oh, Mi-Jin;Oh, Chan-Ho
    • Korean Journal of Pharmacognosy
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    • v.47 no.3
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    • pp.197-203
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    • 2016
  • Decursin is a major component of the root of Angelica gigas(Umbelliferae), which has been traditionally used in Korea as a tonic and to treat anemia, hemiplegia, and women's diseases. The objective of this study is to identify the anti-cancer mechanism induced by decursin on apoptosis of human leukemia and lymphoma cells. Cytotoxicity of decursin on U937, HL-60, MOLT-4, THP-1 cells showed the significant effects. First of all, $IC_{50}$ of decursin on four cell lines was 27.1, 32.4, 17.4, $15.1{\mu}M$, respectively. So $IC_{50}$ in THP-1 cells was the smallest among 4 cell lines treated with decursin($15.1{\mu}M$). In order to understand the apoptosis-mechanism by decursin, we examined the gene expression of bcl-2(anti-apoptotic), bax(pro-apoptotic) and p53(tumor suppressor)after treating the THP-1 cells with decursin(10, 50 and $100{\mu}M$). It was found bcl-2 gene was decreased dose dependently, the expression level of bax gene of THP-1 cells treated with $100{\mu}M$ of decursin was about 3 times higher than those of control, and p53 gene was increased In the same concentration($100{\mu}M$), p53 gene was increased dose dependent manner. In protein express, bcl-2 and p53 protein showed a tendency to decrease. bax was increased about 4 fold. Therefore decursin is a useful chemotherapeutic agent against leukemia.

Long Non-Coding RNA CCAT1 Acts as a Competing Endogenous RNA to Regulate Cell Growth and Differentiation in Acute Myeloid Leukemia

  • Chen, Lianxiang;Wang, Wei;Cao, Lixia;Li, Zhijun;Wang, Xing
    • Molecules and Cells
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    • v.39 no.4
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    • pp.330-336
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    • 2016
  • Long non-coding RNAs (lncRNAs) are involved in multiple cellular events, as well as in tumorigenesis. Colon cance-rassociated transcript-1 (CCAT1) gene encodes an lncRNA whose over-activation was observed in an expanding list of primary human solid tumors and tumor cell lines, however its biological roles in acute myeloid leukaemia (AML) has not been reported yet at present. In this study, the aberrant upregulation of CCAT1 was detected in French-American-British M4 and M5 subtypes of adult AML patients. By gain- and loss-of-function analysis, we determined that CCAT1 repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155. Accordingly, a significant decrease in miR-155 level was detected in AML patients. Reintroduction of miR-155 into HL-60 cells restored monocytic maturation and repressed cell proliferation. Furthermore, CCAT1 could up-regulated c-Myc via its competing endogenous RNA (ceRNA) activity on miR-155. In conclusion, these results revealed new mechanism of lncRNA CCAT1 in AML development, and suggested that the manipulation of CCAT1 expression could serve as a potential strategy in AML therapy.

Effect of Butanol Fraction of Mylabris phalerata on Induction of Apoptosis in U937 cells (반묘 BuOH층의 U937 세포주에 대한 apoptosis유도 효과)

  • 허정은;윤택준;이종수;정진홍;김성훈
    • YAKHAK HOEJI
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    • v.45 no.5
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    • pp.484-490
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    • 2001
  • Mylabris phalerata(MP) is an insect that has been used for the treatment of cancer in oriental medicine. To evaluate the anticancer activity of Mylabris phalerata, We measured the cytotoxicity of Mylabris phalerata solvent fractions such as MC, EA, BuOH and residual layers on U937, human monocytic leukemia cells. Of those fractions BuOH layer of Mylabris phalerata was the most effective with ID$_{50}$ of 140$\mu\textrm{g}$/ml. It effectively caused DNA fragmentation from the concentration of 50$\mu\textrm{g}$/ml, showed apoptotic nucleus by tenets assay and expressed apototic portion stained by Annexin-V. It also induced the activation of caspase-3 and cleavage of the substrate poly (ADP-ribose) polymerase (PARP). These results suggest BuOH layer of Mylabris phalerata exerts anticancer activity by induction of apoptosis via activation of caspase-3 protease.e.

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Effect of Orostachys japonicus on Apoptosis and Autophagy in Human monocytic leukemia Cell line THP-1 via Inhibition of NF-κB and Phosphorylation of p38 MAPK (와송이 인간 백혈병 세포주 THP-1에서 NF-κB 활성 억제와 p38 활성을 통해 세포사멸과 자가포식에 미치는 영향)

  • Joo, Seonghee;Jang, Eungyeong;Kim, Youngchul
    • The Journal of Korean Medicine
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    • v.40 no.2
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    • pp.35-50
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    • 2019
  • Objectives: Orostachys japonicas (O. japonicus) has been known for its anti-tumor effect. In the present study, it was investigated whether O. japonicus EtOH extracts could induce apoptosis and autophagy which are part of the main mechanism related to anti-tumor effect in THP-1 cells. Methods: Cells were treated with various concentrations of O. japonicus EtOH extracts ($0-300{\mu}g/ml$) for 24, 48, and 72h. Cell viability was evaluated by MTS/PMS assay and apoptosis rate was examined by flow cytometry and ELISA assay. The mRNA expression of apoptosis-related genes (Bcl-2, Mcl-1, Survivin, Bax) and autophagy-related gene (mTOR) was evaluated using real-time PCR. The protein expression of Caspase-3, Akt, LC3 II, Beclin-1, Atg5, $NF-{\kappa}B$, p38, ERK was evaluated using western blot analysis. Results: O. japonicus EtOH extracts inhibited cell proliferation and apoptosis rate was increased in both flow cytometry and ELISA assay. Bcl-2, Mcl-1, Survivin (anti-apoptosis factors) mRNA expressions were decreased and Bax (pro-apoptosis factor) mRNA level was increased. mTOR mRNA expressions was decreased and LC3 II protein expressions was increased. Activation of $NF-{\kappa}B$ was decreased and phosphorylation of p38 was increased. Conclusion: O. japonicus is regarded to inhibit cell proliferation, to induce apoptosis and to regulate autophagy-related genes in THP-1 cells via $NF-{\kappa}B$ and p38 MAPK signaling pathway. This suggests O. japonicus could be an effective herb in treating acute myeloid leukemia.