Cytotoxic activity of l-lysine alpha-oxidase against leukemia cells

Author(s):  
Mariana N. Costa ◽  
Roberto N. Silva
1986 ◽  
Vol 72 (5) ◽  
pp. 507-510
Author(s):  
Seema G. Pradhan ◽  
Manik P. Chitnis ◽  
Vathsala S. Basrur ◽  
K. Satyamoorthy ◽  
Suresh H. Advani

The in vitro effect of sintamil, as a modulator alone and in combination with hydroxyurea (HU), on cytotoxicity was studied in 16 cases of human chronic myeloid leukemia (CML). We investigated the cytotoxicity of the drugs as a function of the exposure dose (HU, 10−4 M; sintamil, 10 μg/ml) and the exposure time (1 h) to the agent. Cytotoxicity was evaluated as the inhibition of incorporation of [3H-methyl]thymidine in the nucleic acids of CML cells. Cytotoxicity of HU was greatly enhanced (P < 0.001) by 1 h exposure of the CML cells to sintamil. The present data indicate that sintamil potentiates the cytotoxic activity of HU in CML cells.


2013 ◽  
Vol 8 (12) ◽  
pp. 1934578X1300801
Author(s):  
Mitsuru Satoh ◽  
Yoshio Satoh ◽  
Yasuhiro Anzai ◽  
Daisuke Ajisawa ◽  
Keiichi Matsuzaki ◽  
...  

Two new humulene-type sesquiterpenes, named hyptishumulene I (1) and II (2), have been isolated, together with eight known compounds, a humulene-type sesquiterpene (3), a monoterpene (4) and six abietane-type diterpenoids (5–10) from the aerial parts of Hyptis incana (Labiatae). The cytotoxic activity of the isolated compounds against mouse leukemia cells (L1210) was examined. The abietane-type diterpenoids (5–10) showed rather potent growth inhibitory activity (IC50<15 μM), while the new humulene-type compounds (1 and 2) exhibited moderate activity (IC50>50 μM).


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2385-2385
Author(s):  
Anri Saito ◽  
Miwako Narita ◽  
Norihiro Watanabe ◽  
Ayumi Yokoyama ◽  
Asuka Sekiguchi ◽  
...  

Abstract In order to establish an efficient anti-tumor cellular immunotherapy using blood γδ T cells, we investigated the cytotoxic activity of γδ T cells expanded from patients with leukemia against autologous leukemia cells and explored the potent methods for enhancing the anti-tumor cytotoxic activity of γδ T cells. We clarified that γδ T cells generated from leukemia patients possess the cytotoxic activity against autologous leukemia cells. Besides, anti-tumor cytotoxic activity of expanded γδ T cells was enhanced by the short-term culture of γδ T cells with type I IFN (IFN-α and IFN-β). The sensitivity of target leukemia cells to γδ T cells was enhanced by the exposure of the target cells to bisphosphonate such as zoledronate, which is one of the antigens recognized by γδ T cells and elevates the content of potent antigen for γδ T cells, isoprenyl pyrophosphate (IPP), in tumor cells. Blood γδ T cells were expanded from anti-CD3 microbead-separated T cells or anti-γδ TCR microbead-separated γδ T cells in the patients with acute myelogenous leukemia by the culture with zoledronate and a low concentration of IL-2 for 1–2 weeks. For the activation of expanded γδ T cells, cultured γδ T cells were exposed with type I IFN for 1–3 days. The supernatant prepared from the culture of type I IFN-activated γδ T cells was assayed for cytokine (IFN-γ, TNF-α, IL-4, IL-5, IL-10) concentration by cytometric bead array. Anti-tumor cytotoxicity of γδ T cells was evaluated by 51Cr-release assay by using purified γδ T cells as effector cells and autologous leukemia cells as target cells. In most patients with acute leukemia, γδ T cells could be markedly expanded by the culture with zoledronate and IL-2 and almost all the expanded γδ T cells possessed Vδ2 TCR. Expanded and purified γδ T cells derived from the patients with leukemia were demonstrated to be cytotoxic against autologous leukemia cells. By the culture of expanded γδ T cells with type I IFN, the expression of the activation marker CD69 and the apoptosis molecule Trail was enhanced at the concentration dependent of type I IFN especially IFN-β. The expanded γδ T cells were shown to produce a remarkable amount of IFN-γ and a considerable amount of TNF-α and the cytokine production was increased by the addition of type I IFN. In addition, the cytotoxic activity of γδ T cells was enhanced by incubating target leukemia cells with zoledronate for 1–2 days. The present study demonstrated that γδ T cells expanded from patient’s blood are cytotoxic to patient’s leukemia cells. It is also demonstrated that there are two methods practically available for enhancing the cytotoxic activity of expanded γδ T cells against leukemia cells, one of which is activating γδ T cells by using type I IFN, and the other is elevating the sensitivity of target cells by using bisphosphonate. These findings implied the possibility that type I IFN-activated γδ T cells could be efficiently applied for cellular immunotherapy in the patients with hematological malignancies who is being administered with bisphosphonate. Moreover, in vivo administration of bisphosphpnate, a low dose of IL-2 and type I IFN could be effective for tumors as γδ T cell-based cellular immunotherapy.


1998 ◽  
Vol 55 (8) ◽  
pp. 1229-1234 ◽  
Author(s):  
Hiroyuki Kobayashi ◽  
Yuzuru Takemura ◽  
James F. Holland ◽  
Takao Ohnuma

Author(s):  
M. Sulaiman Zubair ◽  
Subehan Subehan

DNA Topoisomerase II inhibitors are a type of anticancer drugs. These drugs perform their biological activity either by forming a DNA-intercalator-topoisomerase II ternary complex or by inhibiting other enzymes and/or transcription factors that act on DNA. The strong interactions with DNA play a crucial role for their pharmacological properties. Lunacridine, the active principle from Lunasia amara, was known as DNA intercalating Topoisomerase II inhibitor. With the aims to explore the affinity and molecular interaction of lunacridine compound isolated from Lunasia amara with DNA, molecular docking study has been carried out with DNA model using Autodock 4.0 software. Cytotoxicity test on P388 murine leukemia cells was done also using 100, 30, 10, 3 and 1 μg/ml series of lunacridine concentration. The docking result shows that Lunacridine itself could to dock intercalatively between base pairs of DNA and the possibility interaction with adenine, thymine and cytosine by dipole-dipole interaction.  The lowest predicted binding  energy of lunacridine is –6,22 kcal/mol, whereas original ligand bis thiazole is -16,37 kcal/mol. Lunacridine compound itself has less cytotoxic activity on P388 murine leukemia cells with the IC50 value of 39,52 μg/ml or 129,41 μM. The binding energy of lunacridine on DNA higher than original ligand show that the interaction of lunacridine with DNA is not stable afford the less cytotoxic activity. However, based on the IC50 value, lunacridine could be depeloved as anticancer.Key words: docking, lunacridine,  Lunasia amara, cytotoxic, P388 murine leukimia cells.


2017 ◽  
Vol 12 (2) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Akihito Yokosuka ◽  
Satoru Tatsuno ◽  
Takuma Komine ◽  
Yoshihiro Mimaki

Phytochemical investigation of the MeOH extract of the roots and rhizomes of Saposhnikovia divaricata (Umbelliferae) resulted in the isolation of six chromons (1-6) and five polyacetylene derivatives (7-11). Compounds 9 and 11 were isolated from S. divaricate for the first time. The chromon derivatives (1-6) were evaluated for their cytotoxic activity against HL-60 human promyelocytic leukemia cells. Compound 1 (3′- O-angeloylhamaudol) showed the most potent cytotoxic activity with an IC50 value of 4.41 μM and was found to induce apoptotic cell death in HL-60 cells. The loss of mitochondrial membrane potential, release of cytochrome c into the cytoplasm, and activation of caspase-9 in the 1-treated HL-60 cells suggests that 1 induces apoptosis through the mitochondrial-dependent apoptotic pathway.


2008 ◽  
Vol 265 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Manlio Tolomeo ◽  
Stefania Grimaudo ◽  
Antonietta Di Cristina ◽  
Rosaria M. Pipitone ◽  
Luisa Dusonchet ◽  
...  

2016 ◽  
Vol 79 (4) ◽  
pp. 691-696 ◽  
Author(s):  
Paola E. Ordóñez ◽  
Krishan K. Sharma ◽  
Laura M. Bystrom ◽  
Maria A. Alas ◽  
Raul G. Enriquez ◽  
...  

2015 ◽  
Vol 10 (6) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Akihito Yokosuka ◽  
Yoshikazu Koyama ◽  
Yoshihiro Mimaki

Three new isoflavonoid glycosides (1, 5, and 9) and 10 known compounds (2–4, 6–8, and 10–13) were isolated from the underground parts of Iris florentina (Iridaceae). The structures of the new compounds were determined based on extensive spectroscopic data and the results of hydrolytic cleavage. The isolated compounds and the aglycones were evaluated for cytotoxic activity against HL-60 human promyelocytic leukemia cells. Compound 12 induced apoptotic cell death in the HL-60 cells.


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