• YAKHAK HOEJI
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• v.31 no.5
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• pp.253-265
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• 1987

To develop hybridomas secreting monoclonal antibodies to be used as unlimited sources of reagents indispensable for the diagnosis and treatement of leukemic malignancy, a monoclonal antibody was generated to human pre-T leukemia cells (Jurkat). Hybridomas were produced against Jurkat cell line by fusing spleen cells from hyperimmunized mice with murine plasmacytoma cells (P3$\times$63Ag8. V653). One monoclonal antibody derived from this fusion, designated DMJ-2 was reactive with T-cell lines (Jurkat, Molt-4 and RPMI-8402) and normal peripheral E-rosette forming T cells, but unreactive with B-cell lines (Daudi, Nalm-6) and non-T, non-B cell line (K562). Conclusively DMJ-2 reactive with mature and immature T-lineage lymphoid cells.

• Korean Journal of Pharmacognosy
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• v.33 no.1 s.128
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• pp.29-34
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• 2002

Albizzia julibrissin belonging to the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in Oriental traditional medicine. The water extract of A. julibrissin induced apoptosis in Jurkat T-acute lymphoblastic leukemia (ALL) cells as measured by cell morphology. The capability of this herb medicine to induce apoptosis was associated with proteolytic cleavage of specific target protein such as beta-catenin protein suggesting the possible involvement of caspases. The purpose of the present study is also to investigate the effect of A. julibrissin on cell cycle progression. Our results showed that GI checkpoint related gene products (cyclin D1, cyclin dependent kinase 4, retinoblastoma, E2F1) were decreased in their protein levels in a dose-dependent manners after treatment of the extract. These results indicate that the increase of apoptotic cell death by A. julibrissin may be due to the inhibition of cell cycle progression in wild type p53-lacking Jurkat cells.

• YAKHAK HOEJI
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• v.45 no.6
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• pp.730-738
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• 2001

Apoptosis is a morphologically and biochemically distinct form of cell death that occurs in many different cell types in a wide variety of organisms. Ajbizzia julibrissin belonging the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in oriental traditional medicine. This study investigates whether the water extract off julibrissin induce apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Jurkat cells were increased inhibitions of cell viability in a concentration-dependent manner by A julibrissin. This herbal medicine also caused apoptosis as measured by cell morphology and DNA fragmentation. The capability oft julibrissin 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 caspases. Our result skewed that Bcl-2 and Bax protein levels were not changed in all A julibrissin-treated groups compared to control group. These results suggest that A julibrissin-mediated apoptosis is independent with Bcl-2 related signaling pathway in this cells.

• 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]

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.93-100
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• 2014

Background: Curcumin has has been reported to exert anti-inflammatory, anti-oxidation and anti-angiogenic activity in various types of cancer. It has also been shown to induce apoptosis in leukemia cells. We aimed to unravel the role of the redox pathway in Curcumin mediated apoptosis with a panel of human leukemic cells. Materials and Methods: In this study in vitro cytotoxicity of Curcumin was measured by MTT assay and apoptotic effects were assessed by annexin V/PI, DAPI staining, cell cycle analysis, measurement of caspase activity and PARP cleavage. Effects of Curcumin on intracellular redox balance were assessed using fluorescent probes like $H_2DCFDA$, JC1 and an ApoGSH Glutathione Detection Kit respectively. Results: Curcumin showed differential anti-proliferative and apoptotic effects on different human leukemic cell lines in contrast to minimal effects on normal cells. Curcumin induced apoptosis was associated with the generation of intracellular ROS, loss of mitochondrial membrane potential, intracellular GSH depletion, caspase activation. Conclusions: As Curcumin induces programmed cell death specifically in leukemic cells it holds a great promise as a future therapeutic agent in the treatment of leukemia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.6
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• pp.1383-1392
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• 2003

Apoptosis is a morphologically and biochemically district form of cell death that occurs in many different cell types in a wide variety of organisms. Albizzia julibrissin belonging the family Leguminosae has been used for the treatment of contusion, sore throat, amnesia, and insomnia in oriental traditional medicine. This study investigates whether the water extract of A. julibrissin induce apoptotic cell death in Jurkat T-acute lymphoblastic leukemia (ALL) cells. Jurkat cells were increased inhibitions of cell viability in a concentration-dependent manner by A. julibrissin. This herbal medicine also caused apoptosis as measured by cell morphology and DNA fragmentation. The capability of A. julibrissin to induce apoptosis was associated with proteolytic cleavage of specific target proteins such as poly (ADP-ribose)polymerase (PARP) and beta-catenin proteins suggesting the possible involvement of caspases. Our result showed that Bcl-2 and Bax protein levels were not changed in all A. julibrissin-treated groups compared to control group. These results suggest that A. julibrissin-mediated apoptosis is independent with Bcl-2 related signaling pathway in this cells. The purpose of the present study is also to investigate the Effect of A. julibrissin on cell cycle progression. Our results showed that G1 checkpoint related gene products (cyclin D1, cyclin dependent kinase 4, retinoblastoma, E2F1) were decreased in their protein levels in a dose-dependent manners after treatment of the extract. These results indicate that the increase of apoptotic cell death by A. julibrissin may be due to the inhibition of cell cycle progression in wild type p53-lacking Jurkat cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.605-610
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• 2003

According to the Leukemia and Lymphoma Society, leukemia is a malignant disease (cancer) that originates in a cell in the marrow. It is characterized by the uncontrolled growth of developing marrow cells. There are two major classifications of leukemia: myelogenous or lymphocytic, which can each be acute or chronic. The terms myelogenous or lymphocytic denote the cell type involved. Thus, four major types of leukemia are: acute or chronic myelogenous leukemia and acute or chronic lymphocytic leukemia. Leukemia, lymphoma and myeloma are considered to be related cancers because they involve the uncontrolled growth of cells with similar functions and origins. The diseases result from an acquired (not inherited) genetic injury to the DNA of a single cell, which becomes abnormal (malignant) and multiplies continuously. In the United States, about 2,000 children and 27,000 adults are diagnosed each year with leukemia. Treatment for cancer may include one or more of the following: chemotherapy, radiation therapy, biological therapy, surgery and bone marrow transplantation. The most effective treatment for leukemia is chemotherapy, which may involve one or a combination of anticancer drugs that destroy cancer cells. Specific types of leukemia are sometimes treated with radiation therapy or biological therapy. Common side effects of most chemotherapy drugs include hair loss, nausea and vomiting, decreased blood counts and infections. Each type of leukemia is sensitive to different combinations of chemotherapy. Medications and length of treatment vary from person to person. Treatment time is usually from one to two years. During this time, your care is managed on an outpatient basis at M. D. Anderson Cancer Center or through your local doctor. Once your protocol is determined, you will receive more specific information about the drug(s) that Will be used to treat your leukemia. There are many factors that will determine the course of treatment, including age, general health, the specific type of leukemia, and also whether there has been previous treatment. there is considerable interest among basic and clinical researchers in novel drugs with activity against leukemia. the vast history of experience of traditional oriental medicine with medicinal plants may facilitate the identification of novel anti leukemic compounds. In the present investigation, we studied 31 kinds of anti leukemic medicinal plants, which its pharmacological action was already reported through many experimental articles and oriental medical book: 『pharmacological action and application of anticancer traditional chinese medicine』 In summary: Used leukemia cellline are HL60, HL-60, Jurkat, Molt-4 of human, and P388, L-1210, L615, L-210, EL-4 of mouse. 31 kinds of anti leukemic medicinal plants are Panax ginseng C.A Mey; Polygonum cuspidatum Sieb. et Zucc; Daphne genkwa Sieb. et Zucc; Aloe ferox Mill; Phorboc diester; Tripterygium wilfordii Hook .f.; Lycoris radiata (L Her)Herb; Atractylodes macrocephala Koidz; Lilium brownii F.E. Brown Var; Paeonia suffruticosa Andr.; Angelica sinensis (Oliv.) Diels; Asparagus cochinensis (Lour. )Merr; Isatis tinctoria L.; Leonurus heterophyllus Sweet; Phytolacca acinosa Roxb.; Trichosanthes kirilowii Maxim; Dioscorea opposita Thumb; Schisandra chinensis (Rurcz. )Baill.; Auium Sativum L; Isatis tinctoria, L; Ligustisum Chvanxiong Hort; Glycyrrhiza uralensis Fisch; Euphorbia Kansui Liou; Polygala tenuifolia Willd; Evodia rutaecarpa (Juss.) Benth; Chelidonium majus L; Rumax madaeo Mak; Sophora Subprostmousea Chunet T.ehen; Strychnos mux-vomical; Acanthopanax senticosus (Rupr.et Maxim.)Harms; Rubia cordifolia L. Anti leukemic compounds, which were isolated from medicinal plants are ginsenoside Ro, ginsenoside Rh2, Emodin, Yuanhuacine, Aleemodin, phorbocdiester, Triptolide, Homolycorine, Atractylol, Colchicnamile, Paeonol, Aspargus polysaccharide A.B.C.D, Indirubin, Leonunrine, Acinosohic acid, Trichosanthin, Ge 132, Schizandrin, allicin, Indirubin, cmdiumlactone chuanxiongol, 18A glycyrrhetic acid, Kansuiphorin A 13 oxyingenol Kansuiphorin B. These investigation suggest that it may be very useful for developing more effective anti leukemic new dregs from medicinal plants.

• Biomolecules & Therapeutics
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• v.27 no.5
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• pp.492-501
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• 2019

Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T- acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with $10{\mu}M$ up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to $1.94{\mu}M$. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.