Cytotoxic Steroids from The Stem Bark of Chisocheton cumingianus (Meliaceae)

In the course of our continuing search for anticancer compounds from Chisocheton species, three steroids, stigmast-5-en-3β-ol (1), stigmast-5-en-3β-ol-3-O-β-D-glucopyranoside (2) and stigmast-5,22-dien-3β-ol-3-O-β-D-glucopyranoside (3), were obtained from the stembark of Chisocheton celebicus. The structures of compound 1-3 were identified with spectroscopic data including IR, 1D-NMR, 2D-NMR and TOF-MS, as well as by comparing with those spectral data previously. Compounds 1-3, were evaluated for their cytotoxic effects against P-388 murine leukemia cells and displayed the cytotoxicity activity with IC50 values of 12.45 ± 0.050, 52.27 ± 0.031 and 62.52 ± 0.076 µg/mL, respectively.

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Chemical Constituents from the Fungus Antrodia cinnamomea

Natural Product Communications ◽

10.1177/1934578x1901400134 ◽

2019 ◽

Vol 14 (1) ◽

pp. 1934578X1901400

Author(s):

Ming-Der Wu ◽

Ming-Jen Cheng ◽

Yen-Lin Chen ◽

Hsun-Hsuo-Chang ◽

Yueh-Hsiung Kuo ◽

...

Keyword(s):

Solid State ◽

Secondary Metabolites ◽

Cell Lines ◽

Cancer Cell ◽

Spectroscopic Data ◽

Chemical Constituents ◽

Cancer Cell Lines ◽

Cytotoxic Effects ◽

Chemical Structures

A new benzenoid, 4-methoxy-7-methylbenzo[ d][1,3]dioxol-5-ol (1) and three known secondary metabolites 2,3-dimethoxy-5-methyl[1,4]benzoquinone (2), 2-methoxy-6-methyl-1,4-benzoquinone (3) and 5-methyl-benzo[1,3]dioxole-4,7-diol (4) were isolated from the mycelia of A. cinnamomea BCRC 36799 by solid state fermentation with adlay. Their chemical structures were elucidated on the basis of HRESIMS, NMR spectroscopic data and comparison with reported values. All isolated compounds 1–4 were tested for their cytotoxicity against the six cancer cell lines using the MTT assay. Among them, compound 3 displayed significant cytotoxic effects toward all six tested cancer cell lines, with IC50 values ranging from 2.8–8.7 μM in vitro.

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Ergosterol Peroxide and Stigmasterol from The Stembark of Aglaia simplicifolia (Meliaceae) and Their Cytotoxic against HeLa Cervical Cancer Cell Lines

Jurnal Kimia VALENSI ◽

10.15408/jkv.v1i1.20068 ◽

2021 ◽

Vol 1 (1) ◽

pp. 46-51

Author(s):

Nunung Kurniasih ◽

Asep Supriadin ◽

Desi Harneti ◽

Rizky Abdulah ◽

Mohamad Nurul Azmi bin Mohamad Taib ◽

...

Keyword(s):

Cervical Cancer ◽

2D Nmr ◽

Cytotoxic Effects ◽

Cytotoxicity Activity ◽

Chemical Structures ◽

Ergosterol Peroxide ◽

Cervical Cancer Cells ◽

Ic50 Values ◽

Hela Cervical Cancer Cell

Two steroid compounds, ergosterol peroxide (1) and stigmasterol (2) have been isolated from the stembark of Aglaia simplicifolia belong to Meliaceae family. The chemical structures of 1 and 2 were identified based on spectroscopic evidence including UV, IR, 1D NMR, 2D NMR as well as mass spectra and by comparison with those previously reported spectra data. Both compounds were evaluated for their cytotoxic effects against cervical cancer HeLa cells in vitro. Compounds 1 and 2 showed cytotoxicity activity against HeLa cervical cancer cells with IC50 values of 0.80 and 26.42 µM, respectively.

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Ergosterol Peroxide and Stigmasterol from The Stembark of Aglaia simplicifolia (Meliaceae) and Their Cytotoxic against HeLa Cervical Cancer Cell Lines

Jurnal Kimia VALENSI ◽

10.15408/jkv.v7i1.20068 ◽

2021 ◽

Vol 7 (1) ◽

pp. 46-51

Author(s):

Nunung Kurniasih ◽

Asep Supriadin ◽

Desi Harneti ◽

Rizky Abdulah ◽

Mohamad Nurul Azmi bin Mohamad Taib ◽

...

Keyword(s):

Cervical Cancer ◽

2D Nmr ◽

Cytotoxic Effects ◽

Cytotoxicity Activity ◽

Chemical Structures ◽

Ergosterol Peroxide ◽

Cervical Cancer Cells ◽

Ic50 Values ◽

Hela Cervical Cancer Cell

Two steroid compounds, ergosterol peroxide (1) and stigmasterol (2) have been isolated from the stembark of Aglaia simplicifolia belong to Meliaceae family. The chemical structures of 1 and 2 were identified based on spectroscopic evidence including UV, IR, 1D NMR, 2D NMR as well as mass spectra and by comparison with those previously reported spectra data. Both compounds were evaluated for their cytotoxic effects against cervical cancer HeLa cells in vitro. Compounds 1 and 2 showed cytotoxicity activity against HeLa cervical cancer cells with IC50 values of 0.80 and 26.42 µM, respectively.

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Aryl Maleimides as Apoptosis Inducers on L5178-Y Murine Leukemia Cells (in silico, in vitro and ex vivo Study)

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520615666160504094417 ◽

2016 ◽

Vol 16 (12) ◽

pp. 1615-1621 ◽

Cited By ~ 3

Author(s):

Erik Andrade-Jorge ◽

Marycarmen Godínez-Victoria ◽

Luvia Enid Sánchez-Torres ◽

Luis Humberto Fabila-Castillo ◽

José G. Trujillo-Ferrara

Keyword(s):

In Silico ◽

Ex Vivo ◽

Leukemia Cells ◽

Ex Vivo Study ◽

Murine Leukemia

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Solanum lyratumExtracts Induce Extrinsic and Intrinsic Pathways of Apoptosis in WEHI-3 Murine Leukemia Cells and Inhibit Allograft Tumor

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/254960 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 17

Author(s):

Jai-Sing Yang ◽

Chia-Chun Wu ◽

Chao-Lin Kuo ◽

Yu-Hsuan Lan ◽

Chin-Chung Yeh ◽

...

Keyword(s):

Antitumor Activity ◽

Molecular Mechanisms ◽

Fas Ligand ◽

Leukemia Cells ◽

Cycle Arrest ◽

Phase Arrest ◽

Apoptotic Pathways ◽

Murine Leukemia

We investigated the molecular mechanisms of cell cycle arrest and apoptotic death induced bySolanum lyratumextracts (SLE) or diosgenin in WEHI-3 murine leukemia cellsin vitroand antitumor activityin vivo. Diosgenin is one of the components of SLE. Our study showed that SLE and diosgenin decreased the viable WEHI-3 cells and inducedG0/G1phase arrest and apoptosis in concentration- or time-dependent manners. Both reagents increased the levels of ROS production and decreased the mitochondrial membrane potential (ΔΨm). SLE- and diosgenin-triggered apoptosis is mediated through modulating the extrinsic and intrinsic signaling pathways. Intriguingly, the p53 inhibitor (pifithrin-α), anti-Fas ligand (FasL) mAb, and specific inhibitors of caspase-8 (z-IETD-fmk), caspase-9 (z-LEHD-fmk), and caspase-3 (z-DEVD-fmk) blocked SLE- and diosgenin-reduced cell viability of WEHI-3 cells. Thein vivostudy demonstrated that SLE has marked antitumor efficacy against tumors in the WEHI-3 cell allograft model. In conclusion, SLE- and diosgenin-inducedG0/G1phase arrest and triggered extrinsic and intrinsic apoptotic pathways via p53 activation in WEHI-3 cells. SLE also exhibited antitumor activityin vivo. Our findings showed that SLE may be potentially efficacious in the treatment of leukemia in the future.

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Leukemia regression by vascular disruption and antiangiogenic therapy

Blood ◽

10.1182/blood-2009-06-230474 ◽

2010 ◽

Vol 116 (9) ◽

pp. 1539-1547 ◽

Cited By ~ 53

Author(s):

Gerard J. Madlambayan ◽

Amy M. Meacham ◽

Koji Hosaka ◽

Saad Mir ◽

Marda Jorgensen ◽

...

Keyword(s):

Antiangiogenic Therapy ◽

Leukemia Cell ◽

Leukemia Cells ◽

Vascular Endothelial ◽

Vascular Disrupting Agent ◽

Cytotoxic Effects ◽

Vascular Disruption ◽

Acute Myelogenous ◽

Endothelial Growth Factor

Acute myelogenous leukemias (AMLs) and endothelial cells depend on each other for survival and proliferation. Monotherapy antivascular strategies such as targeting vascular endothelial growth factor (VEGF) has limited efficacy in treating AML. Thus, in search of a multitarget antivascular treatment strategy for AML, we tested a novel vascular disrupting agent, OXi4503, alone and in combination with the anti-VEGF antibody, bevacizumab. Using xenotransplant animal models, OXi4503 treatment of human AML chloromas led to vascular disruption in leukemia cores that displayed increased leukemia cell apoptosis. However, viable rims of leukemia cells remained and were richly vascular with increased VEGF-A expression. To target this peripheral reactive angiogenesis, bevacizumab was combined with OXi4503 and abrogated viable vascular rims, thereby leading to enhanced leukemia regression. In a systemic model of primary human AML, OXi4503 regressed leukemia engraftment alone and in combination with bevacizumab. Differences in blood vessel density alone could not account for the observed regression, suggesting that OXi4503 also exhibited direct cytotoxic effects on leukemia cells. In vitro analyses confirmed this targeted effect, which was mediated by the production of reactive oxygen species and resulted in apoptosis. Together, these data show that OXi4503 alone is capable of regressing AML by a multitargeted mechanism and that the addition of bevacizumab mitigates reactive angiogenesis.

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Cytotoxic Effects of CML28 Specific T Cells on Acute Leukemia Cells In Vitro.

Blood ◽

10.1182/blood.v110.11.4886.4886 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4886-4886

Author(s):

Hanwen Mao ◽

Wenli Liu ◽

Zhe Gen ◽

Wei Huang ◽

Yicheng Zhang ◽

...

Keyword(s):

T Cells ◽

Acute Leukemia ◽

Mononuclear Cells ◽

Antigen Presenting Cells ◽

Leukemia Cells ◽

Cytotoxic Effects ◽

Artificial Antigen ◽

Leukemia Treatment ◽

Antigen Presenting

Abstract The antigen-specific cytotoxic T lymphocyte activated by antigen presenting cell is widely used in cell immunotherapy recently. CML28, which was screened from chronic myelogenous leukemia (CML) patients, was reported to be a specific tumour antigen and over-expressed on CML cells and acute leukemia cells. Therefore, CML28 could be a potential target for leukemia treatment. Dendritic cells (DC) are the most important antigen present cells, but it is hard to isolate and culture DCs for clinical use, which hampers the specific cell immunotherapy. Our investigation aimed to study the cytotoxic effects of CML28 specific T cells activated by artificial antigen presenting cells, on acute leukemia cells in vitro. Artificial antigen presenting cells were prepared by connecting CML28 to magnetic superbead that containing HLA-A2-Ig and B7-1 molecule. Mononuclear cells were isolated from the bone marrow or peripheral blood of healthy donors with positive HLA-A2. The artificial antigen-presenting cells were co-cultured with isolated mononuclear cells for four weeks. The activation and proliferation of CML28-specific T cells were measured by dimmer binding technique using flow cytometry. The cytotoxic effects of CML28-specific T cells on leukemia cells, which were isolated from leukemia patient, were evaluated by lactate dehydrogenase (LDH) releasing assay. Increased proportion of CML28-specific T cells was observed in artificial antigen-presenting group than in control group (29.27±3.54% vs 2.95±0.66%, p<0.05). For cytotoxic effects assay, significant higher killing efficiency was seen in artificial antigen-presenting group (41.47±4.23%vs3.56±0.71%, when the effector: target ration is 40:1, p<0.01). Therefore, we concluded that the artificial antigen presenting cells could mimic antigen presenting cells to induce specific T cell activation and proliferation, and cytotoxic effects on target cells, indicating that artificial antigen presenting cell-induced cytotocix T cells could be an option for leukemia treatment.

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In vitro generation of tumor-specific cytotoxic lymphocytes. Secondary allogeneic mixed tumor lymphocyte culture of normal murine spleen cells

Journal of Experimental Medicine ◽

10.1084/jem.146.2.468 ◽

1977 ◽

Vol 146 (2) ◽

pp. 468-482 ◽

Cited By ~ 58

Author(s):

S Gillis ◽

KA Smith

Keyword(s):

Cell Surface ◽

Lymphocyte Culture ◽

Leukemia Cells ◽

Cytotoxic Lymphocytes ◽

Mixed Tumor ◽

Spleen Cells ◽

Syngeneic Tumor ◽

Murine Spleen ◽

Murine Leukemia

In vivo or in vitro immunity to murine leukemia virus (MuLV)-induced leukemia cells which do not effectively produce virus, has been difficult to demonstrate. Because immunizations with allogeneic murine leukemia cells have been used to confer syngeneic tumor immunity to virus- producing cells, we attempted to generate lymphocytes, cytotoxic to syngeneic nonproducer leukemia cells, by stimulating normal murine spleen cells with allogeneic nonproducer leukemia cells in mixed tumor lymphocyte culture (MTLC) reactions in vitro. Secondary allogeneic MTLC of normal C57BL/6 or DBA/2 spleen cells effectively produced syngeneic tumor-specific cytotoxic lymphocytes. Target cells lysed in lymphocyte- mediated cytolysis (LMC) assays, included both Friend and Rauscher virus- induced syngeneic murine leukemia cells and chemically-induced hematopoietic tumor cells. Syngeneic tumor cells were lysed regardless of whether they produced infectious MuLV or expressed viral antigens gp-71, p-30, or p-12 at the cell surface. Syngeneic normal cells (thymus, lymph node, or Concanavalin A-stimulated spleen cells) used as targets in LMC assays were uneffected by lymphocytes harvested from secondary allogeneic MTLC. Several other in vitro culture treatments including secondary syngeneic MTLC and repetitive mixed lymphocyte culture stimulations were incapable of generating tumor-specific cytotoxic lymphocytes. Based upon these results, we propose that secondary MTLC stimulation of normal spleen cells with allogeneic nonproducer leukemia cells selects for the proliferation of two subpopulations of antigen-specific cytotoxic lymphocytes. The population capable of effecting syngeneic tumor cell lysis is directed against tumor-associated cell surface antigens which may be distinct from viral structural proteins or glycoproteins. The growth of these tumor-specific cytotoxic lymphocytes may be enhanced by a soluble allogeneic effect factor produced by the proliferation of the second subpopulation of lymphocytes generated in repetitive allogeneic MTLC, namely those lymphocytes with specificities directed against differing histocompatibility antigens.

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In Vitro Assessment of Anthelmintic Activities ofRauwolfia vomitoria(Apocynaceae) Stem Bark and Roots against Parasitic Stages ofSchistosoma mansoniand Cytotoxic Study

Journal of Parasitology Research ◽

10.1155/2017/2583969 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Emmanuel Mouafo Tekwu ◽

Kwabena Mante Bosompem ◽

William Kofi Anyan ◽

Regina Appiah-Opong ◽

Kofi Baffour-Awuah Owusu ◽

...

Keyword(s):

Neglected Tropical Diseases ◽

Anthelmintic Activity ◽

Stem Bark ◽

Assay Method ◽

Cytotoxic Effects ◽

Chang Liver Cell ◽

Plant Parts ◽

In Vitro Assessment ◽

Rauwolfia Vomitoria

Schistosomiasis is a Neglected Tropical Diseases which can be prevented with mass deworming chemotherapy. The reliance on a single drug, praziquantel, is a motivation for the search of novel antischistosomal compounds. This study investigated the anthelmintic activity of the stem bark and roots ofRauwolfia vomitoriaagainst two life stages ofSchistosoma mansoni. Both plant parts were found to be active against cercariae and adult worms. Within 2 h of exposure all cercariae were killed at a concentration range of 62.5–1000 µg/mL and 250–1000 µg/mL ofR. vomitoriastem bark and roots, respectively. The LC50values determined for the stem bark after 1 and 2 h of exposure were 207.4 and 61.18 µg/mL, respectively. All adult worms exposed to the concentrations range of 250–1000 µg/mL for both plant parts died within 120 h of incubation. The cytotoxic effects against HepG2 and Chang liver cell assessed using MTT assay method indicated that both plant extracts which were inhibitory to the proliferation of cell lines with IC50> 20 μg/mL appear to be safe. This report provides the first evidence of in vitro schistosomicidal potency ofR. vomitoriawith the stem bark being moderately, but relatively, more active and selective against schistosome parasites. This suggests the presence of promising medicinal constituent(s).

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