• Korean Journal of Pharmacognosy
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• v.32 no.4 s.127
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• pp.274-279
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• 2001

Ailanthus altissima belonging to the family Simaroubaceae has been used to settle an upset stomach, to combat a fever, and as an insecticide. Apoptosis is an active process, which is a critical feature of the regulated development of multicellular organisms. We investigated whether the extract of A. altissima induced apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Upon treatments with the extract, the dose-dependent inhibitions of cell viability were observed. It also caused apoptosis as measured by cell morphology and DNA fragmentation. The capability of the extract to induce apoptosis was associated with proteolytic cleavage of specific target protein such as poly(ADP-ribose)polymerase (PARP) protein, suggesting the possible involvement of the activations of caspases. Further study showed that Bcl-2 protein levels were not changed in all treated groups compared to control group. These results suggest that A. altissima induces Bcl- 2-independent apoptosis in Jurkat T cells.

• Journal of Life Science
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• v.19 no.2
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• pp.163-168
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• 2009

To understand cytotoxic activity of Rubia cordifolia L. (Rubiaceae), which has been used as a traditional oriental medicine, the mechanism underlying cytotoxic effect of its extract on human acute Jurkat T cells was investigated. The methanol extract of roots (3 kg) of R. codifolia was evaporated, dissolved in water, and then extracted by dichloromethane. The substances in the chloroform extract showing the most cytotoxic activity were further purified by a series of preparative HPLC. The extracted active substance (65 mg) was designated as CCH1. When Jurkat T cells were treated with CCH1 at concentration ranging from 0.5 to 2.0 ${\mu}g$/ml, apoptotic phenomena of cells companying several subsequent biochemical reactions such as mitochondria cytochrome c release, activation of casapase-8, -9, and caspase- 3, degradation of PARP and DNA fragmentation occurred via mitochondria-dependent pathway. However, abrogation of apoptosis was observed in an ectopic expression of Bcl-xL, which is a suppressor for mitochondrial cytochrome c release. These results demonstrate that the cytotoxicity of CCH1 against Jurkat T cells is attributable to apoptosis mediated by mitochodria-dependent death-signaling regulated by Bcl-xL. In addition, the CCH1 is more potent to leukemia Jurkat T cell than to human peripheral blood monocyte cells (PBMC).

• Journal of Ginseng Research
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• v.44 no.5
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• pp.725-737
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• 2020

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and the PI3K/Akt/mTOR signaling pathway is activated in most patients with T-ALL and responsible for poor prognosis. 20(S)-Ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anticancer mechanisms of 20(S)-GRh2 targeting the PI3K/Akt/mTOR pathway in T-ALL have not been explored. Methods: Cell growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis, and autophagy. Results: In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at the G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species generation and upregulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, the PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in the spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. Conclusion: These findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.

• Journal of Microbiology and Biotechnology
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• v.12 no.6
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• pp.950-956
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• 2002

The antitumor activity of the insect pathogenic fungus Paecilomyces japonica has been attributed to apoptotic cell death. However, the mechanism underlying the induced apoptosis has not yet been elucidated. In this study, we for the first time show that mitochondria-dependent caspase-3 activation were associated with the apoptotic activity of P. japonica in human acute leukemia Jurkat T cells. When Jurkat T cells were treated with the ethyl acetate extract of P japonica at concentrations ranging from $2-6{\mu}g/ml$, apoptotic cell death. accompanied by several biochemical events such as caspase-9 activation, caspase-3 activation, degradation of poly (ADP-ribose) polymerase (PARP), and apoptotic DNA fragmentation, was induced in a dose-dependent manner. In addition, the release of cytochrome c from mitochondria was detected. Under these conditions, the expression of Fas and Fas-ligand (FasL) remained unchanged. Ethyl acetate extract-induced mitochondrial cytochrome c release, caspase-3 activation, PARP cleavage, and apoptotic DNA fragmentation were suppressed by the ectopic expression of Bcl-2, which is known to block mitochondrial cytochrorme c release. Accordingly, these results demonstrate that P. japonica-induced apoptotic cell death is mediated by a cytochrome c-dependent caspase-3 activation pathway that can be interrupted by Bcl-2.

• Journal of Life Science
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• v.13 no.1
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• pp.118-127
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• 2003

$\rho$-Fluorophenylalanine (FPA), a phenylalanine analog, is able to induce apoptotic cell death of human acute leukemia Jurkat T cells. To better understand the mechanism by which FPA induces apoptotic cell death, the effect of ectopic expression of antiapoptotic proteins, Bcl-2 and Bcl-xL, on FPA-induced apoptosis was investigated by employing lurkat T cells transfected with Bcl-2 gene (JT/Bcl-2) or Bcl-xL gene (1/Bcl-xL) and Jurkat T cells transfected with vector (JT/Neo or J/Neo). When Jurkat T cells, JT/Neo or J/Neo, were exposed to FPA at concentrations ranging from 0.63 to 5.0 mM, the cell viability determined by MTT assay declined in a dose-dependent manner. In addition, apoptotic DNA fragmentation along with several apoptotic events such as caspase-8 activation, Bid cleavage, mitochondrial cytochrome c release, caspase-9 activation, caspase-3 activation, and degradation of PARP was induced. However, the FPA-induced cytotoxic effect, activation of caspase-8, and cleavage of Bid were significantly abrogated by ectopic expression of Bcl-2 or Bcl-xL. At the same time, there was marked reduction in the level of cytochrome c release from mitorhondria, caspase-9 activation, caspase-3 activation, and degradation of PARP. These results indicate that caspase-8 activation, Bid cleavage, and mitochondrial cytochrome c release with subsequent activation of the caspase cascade are negatively regulated by Bcl-2 or Bcl-xL, and are thus required for FPA-induced apoptosis in Jurkat T cells

• The Korean Journal of Mycology
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• v.27 no.4 s.91
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• pp.312-317
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• 1999

In order to study the antitumoral effect of meju extracts, which was made with a single inoculum of the microorganism, the cytotoxicity effects on several human leukemia cells such as promyelocytic leukemia cell (HL60), histiocytic lymphoma cell (U937) and acute T-cell leukemia Jurkat cell, and lymphocyte were analyzed by MTT assay. Twenty one microbes, mainly fungal genera, were isolated from Korean traditional mejus of different regions. From those collected isolates, meju was manufactured and extracted with 80% methanol, respectively. Meju methanol extracts exhibited low activites in cytotoxicity tests on HL60 cell, but high antitumoral effects of meju methanol extracts were shown on U937 and Jurkat cells. Meju methanol extracts made with a genera of Mucor, Absidia and Aspergillus showed prominant cytotoxic activities, especially. However all these extracts had no inhibitory effects on the cell growth of lymphocyte under the same conditions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.5
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• pp.1337-1342
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• 2004

The purpose of this research was to investigate the immunoregulatory effect and the leukemia cell apoptosis of EtOH extract of OGAPI(OGP). The proliferation of cultured splenocytes, thymocytes and mesenteric lymph node cells were enhanced by the addition of OGP. Splenic and thymic T lymphocytes, especially TH and Tc cells were significantly increased in OGP-administered mice. OGP markedly increased the production of γ-interferon in mice serum and accelerated the phagocytic activity in peritoneal macrophages. OGP treatment enhanced the apoptosis of L1210 mouse leukemia and Jurkat, Molt4 human leukemia cells, and increased the expression of apoptosis-related ICE, c-myc, p53 gene in Jurkat cell. These results suggest that OGP have an immunoregulatory action and anti-cancer activity.

• Journal of Life Science
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• v.18 no.11
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• pp.1499-1506
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• 2008

To examine antitumor activity of the edible plant Zanthoxylum schinifolium, the cytotoxic effect of various organic solvent extracts of its stems on human acute leukemia Jurkat T cells was investigated. Among these extracts such as methanol extract (SS-7), methylene chloride extract (SS-8), ethyl acetate extract (SS-9), n-butanol extract (SS-10), and residual fraction (SL-11), SS-8 exhibited the most cytotoxic activity against Jurkat T cells. The methylene chloride extract (SS-8) possessed the apoptogenic activity capable of inducing sub-G1 peak along with apoptotic DNA fragmentation in Jurkat T cells. Western blot analysis revealed that SS-8 induced apoptosis via mitochondrial cytochrome c release into cytoplasm, subsequent activation of caspase-9 and caspase-3, and cleavage of PARP, which could be blocked by overexpression of Bcl-xL. Jurkat T cell clone I2.1 $FADD^{-/-}$) and Jurkat T cell clone I9.2 (caspase-$8^{-/-}$ were as sensitive as was the wild-type Jurkat T cell clone A3 to the cytotoxic effect of SS-8, suggesting no contribution of Fas/FasL system to the SS-8-mediated apoptosis. The GC-MS analysis of SS-8 showed that it was composed of 16 ingredients including 9,12-octadecanoic acid (18.62%), 2,4-dihydro-5-methyl-4- (1-methylethylidene)- 2-(4-nitrophenyl)-3H- pyrazol-3-one (14.97%), hexadecanoic acid (14.23%), (z,z)-6,9-pentadecadien- 1-ol (13.73%), 5,6-dimethoxy-2-methyl benzofuran (10.95%), and 4-methoxy-2-methylcinnamic acid (5.38%). These results demonstrate that the methylene chloride extract of the stems of Z. schinifolium can induce apoptotic cell death in Jurkat T cells via intrinsic mitochondria-dependent caspase cascade regulated by Bcl-xL without involvement of the Fas/FasL system.

• BMB Reports
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• v.45 no.2
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• pp.85-90
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• 2012

Our previous study demonstrated that CopA3, a disulfide dimer of the coprisin peptide analogue (LLCIALRKK), has antibacterial activity. In this study, we assessed whether CopA3 caused cellular toxicity in various mammalian cell lines. CopA3 selectively caused a marked decrease in cell viability in Jurkat T, U937, and AML-2 cells (human leukemia cells), but was not cytotoxic to Caki or Hela cells. Fragmentation of DNA, a marker of apoptosis, was also confirmed in the leukemia cell lines, but not in the other cells. CopA3-induced apoptosis in leukemia cells was mediated by apoptosis inducing factor (AIF), indicating induction of a caspase-independent signaling pathway.

• BMB Reports
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• v.49 no.1
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• pp.63-68
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• 2016

The serine/threonine kinase mTOR is essential for the phosphoinositide 3-kinases (PI3K) signaling pathway, and regulates the development and function of immune cells. Aberrant activation of mTOR signaling pathway is associated with many cancers including leukemia. Here, we report the contributions of mTOR signaling to growth of human leukemic cell lines and mouse T-cell acute leukemia (T-ALL) cells. Torin, an ATP-competitive mTOR inhibitor, was found to have both cytotoxic and cytostatic effects on U-937, THP-1, and RPMI-8226 cells, but not on Jurkat or K-562 cells. All cells were relatively resistant to rapamycin even with suppressed activity of mTOR complex 1. Growth of T-ALL cells induced by Notch1 was profoundly affected by torin partially due to increased expression of Bcl2l11 and Bbc3. Of note, activation of Akt or knockdown of FoxO1 mitigated the effect of mTOR inhibition on T-ALL cells. Our data provide insight on the effect of mTOR inhibitors on the survival and proliferation of leukemic cells, thus further improving our understanding on cell-context-dependent impacts of mTOR signaling. [BMB Reports 2016; 49(1): 63-68]