Resveratrol as an Antitumor Agent In Vivo

Platinum-thymine has been found to be a potent antitumor agent, which is quite soluble in water, and lack nephrotoxicity as the dose-limiting factor. The drug has been shown to interact with DNA and inhibits DNA, RNA and protein synthesis in mammalian cells in vitro. This investigation was undertaken to elucidate the cytotoxic effects of piatinum-thymine on sarcoma-180 cells in vitro ultrastructurally, Sarcoma-180 tumor bearing mice were treated with intraperitoneal injection of platinum-thymine 40mg/kg. A concentration of 60μg/ml dose of platinum-thymine was used in in vitro experiments. Treatments were at varying time intervals of 3, 7 and 21 days for in vivo experiments, and 30, 60 and 120 min., 6, 12, and 24th in vitro. Controls were not treated with platinum-thymine.Electron microscopic analyses of the treated cells in vivo and in vitro showed drastic cytotoxic effect.

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Antitumor Effect of Zwitterions of Imidazolium Derived from L-methionine in BALB/c Mice with Lymphoma L5178Y

Medicinal Chemistry ◽

10.2174/1573406415666191206093754 ◽

2020 ◽

Vol 17 (1) ◽

pp. 33-39

Author(s):

Karen C. Vargas-Castro ◽

Ana M. Puebla Pérez ◽

Irma I. Rangel-Salas ◽

Jorge I. Delgado-Saucedo ◽

José B. Pelayo-Vázquez ◽

...

Keyword(s):

Gold Nanoparticles ◽

Antitumor Activity ◽

Antitumor Agent ◽

Inhibitory Effect ◽

Stabilizing Agent ◽

Biological Compatibility ◽

In Vivo Tests ◽

Antitumoral Agent ◽

Group 1

Background: In the therapy of cancer, several treatments have been designed using nanomaterials, among which gold nanoparticles (AuNPs) have been featured as a promising antitumoral agent. Our research group has developed the synthesis of gold nanoparticles L-AuNPs and D-AuNPs stabilized with zwitterions of imidazolium (L-1 and D-1) derived from L-methionine and D-methionine. Because the stabilizer agent is chiral, we observed through circular dichroism that AuNPs also present chirality; such chirality as well as the fact that the stabilizing agent contains fragments of methionine and imidazolium that are commonly involved in biological processes, opens up the possibility that this system may have biological compatibility. Additionally, the presence of methionine in the stabilizing agent opens the application of this system as a possible antitumor agent because methionine is involved in methylation processes of molecules such as DNA. Objective: The aim of this research is the evaluation of the antitumor activity of gold nanoparticles stabilized with zwitterions of imidazolium (L-AuNPs) derived from L-methionine in the model of BALB/c mice with lymphoma L5178Y. Methods: Taking as a parameter cell density, the evaluation of the inhibitory effect of L-AuNPs was carried out with a series of in vivo tests in BALB/c type mice; three groups of five mice each were formed (Groups 1, 2 and 3); all mice were i.p. inoculated with the lymphoblast murine L5178Y. Group 1 consisted of mice without treatment. In the Groups 2 and 3 the mice were treated with L-AuNPs at 0.3 mg/Kg on days 1, 7 and 14 by orally and intraperitonally respectively. Results: These results show low antitumor activity of these gold nanoparticles (L-NPsAu) but interestingly, the imidazolium stabilizing agent of gold nanoparticle (L-1) displayed promising antitumor activity. On the other hand, the enantiomer of L-1, (D-1) as well as asymmetric imidazole derivate from L-methionine (L-2), do not exhibit the same activity as L-1. Conclusion: The imidazolium stabilizing agent (L-1) displayed promising antitumor activity. Modifications in the structure of L-1 showed that, the stereochemistry (like D-1) and the presence of methionine fragments (like L-2) are determinants in the antitumor activity of this compound.

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A potential antitumor agent, (6-amino-1-methyl-5-nitrosouracilato-N3)-triphenylphosphine-gold(I): Structural studies and in vivo biological effects against experimental glioma

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2013.03.067 ◽

2013 ◽

Vol 64 ◽

pp. 260-272 ◽

Cited By ~ 12

Author(s):

Nuria A. Illán-Cabeza ◽

Antonio R. García-García ◽

José M. Martínez-Martos ◽

María J. Ramírez-Expósito ◽

Tomás Peña-Ruiz ◽

...

Keyword(s):

Biological Effects ◽

Antitumor Agent ◽

Structural Studies ◽

Experimental Glioma ◽

Potential Antitumor

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Phenotypic and Functional Effects of Perifosine on Dendritic Cells.

Blood ◽

10.1182/blood.v110.11.4803.4803 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4803-4803

Author(s):

Weihua Song ◽

Teru Hideshima ◽

Yu-Tzu Tai ◽

Kenneth C. Anderson ◽

Nikhil C. Munshi

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Annexin V ◽

Antitumor Agent ◽

Dependent Manner ◽

Immune Functions ◽

Akt Inhibitor ◽

Antitumor Effects

Abstract Perifosine is a synthetic novel alkylphospholipid, a new class of antitumor agent which targets cell membranes and inhibits Akt activation. Perifosine inhibits multiple myeloma (MM) cell growth in vitro and in vivo mouse model. Currently perifosine is under the evaluation of phase II clinical trail in MM. Although perifosine has shown significant direct antitumor effects, its effect on immune system has not yet been clarified. The objective of this study is to evaluate the effects of perifosine on the activity of antigen presenting cells (APCs). Monocyte-derived dendritic cells (DCs) from normal human donors were used as the APCs, and mature DCs were obtained by the treatment of TNF-α and IL-1β. Perifosine was used at the concentrations of 2.5 uM, 5 uM and 10 uM for the treatment with DCs. We first evaluated the effect of perifosine on the survival of DCs. We observed that the perifosine treatment up to 48 hours had no effect on viability (>90%) of DCs, assessed by annexin V and PI staining. Alteration of phenotype by perifosine on DCs was further examined by flow cytometry. Our results demonstrated that with dose-dependent manner, perifosine led to a significant down-regulation of surface antigens on immature DCs at 24 and 48 hours, which associated to costimulation (CD40, CD80 and CD86), antigen presentation (HLA-ABC, HLA-DPQR) and maturation (CD83). However, we did not observed significant effect of perifosine on above surface markers on mature DCs. Since DCs play a crucial role on the regulation of Th1/Th2 immune responses by the production of IL-12, we next evaluated IL-12 secretion by DCs with and without perifosine treatment. Importantly, treatment with perifosine significantly decreased LPS-induced-IL-12 production, compared to untreated DCs (untrt vs. trt = 192.29 vs. 166.23 pg/ml (2.5uM), 111.19 pg/ml (5uM) and 44.886 pg/ml (10uM)) at 24 hours. To assess the effect of perifosine on DCs function on the regulation of T cell responses, we stimulated allogenic T cells with mature DCs with or without the pre-treatment of perifosine. The proliferation assay by 3H-TdR incorporation and IFN-γ production by ELISA indicated perifosine-treated DCs had no significant effect on the regulation of T cells function. Taken together, these results showed that DCs function are influenced by the treatment of perifosine. Our pre-clinical data therefore indicates the need to monitor immune functions in patients under the Akt inhibitor treatment.

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In vivo hydroxylation of the alkaloid acronine, an experimental antitumor agent

Journal of Medicinal Chemistry ◽

10.1021/jm00299a025 ◽

1970 ◽

Vol 13 (5) ◽

pp. 904-909 ◽

Cited By ~ 26

Author(s):

Hugh Richard Sullivan ◽

Billings Ruth E. ◽

John L. Occolowitz ◽

Harold E. Boaz ◽

Frederick J. Marshall ◽

...

Keyword(s):

Antitumor Agent

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The effect of lipid derivative of anti-tumor drug sarcolysin embedded in phospholipid nanoparticles in the experiments in vivo

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20216706491 ◽

2021 ◽

Vol 67 (6) ◽

pp. 491-499

Author(s):

Yu.A. Tereshkina ◽

T.I. Torkhovskaya ◽

M.A. Sanzhakov ◽

L.V. Kostryukova ◽

Yu.Yu. Khudoklinova ◽

...

Keyword(s):

Mammary Gland ◽

Antitumor Agent ◽

Mouse Mammary Gland ◽

Lymphocytic Leukemia ◽

Pharmacokinetic Parameters ◽

Tumor Growth Inhibition ◽

Phospholipid Nanoparticles ◽

Lipid Derivative ◽

Ld50 Value

To improve the therapeutic properties of the antitumor agent Sarcolysin, we have previously developed and characterized a dosage form representing its ester conjugate with decanol embedded in ultra-small phospholipid nanoparticles less than 30 nm in size (“Sarcolysin-NP”). The effect of the resulting composition was investigated in vivo in comparison with the free substance of sarcolysin. The composition intravenous administration to mice showed an improvement in the pharmacokinetic parameters of sarcolysin associated with its initial higher (by 22%) level in the blood and prolonged circulation, which was also observed in mice with P388 tumor. In mice with three types of tumors — lymphocytic leukemia P388, lymphocytic leukemia L1210, and adenocarcinoma of the mammary gland Ca755 — administration of two doses of sarcolysin over a period of 7 days showed its predominant antitumor effect. The maximum tumor growth inhibition was noted for lymphocytic leukemia L1210 and adenocarcinoma of the mouse mammary gland Ca755 (at a dose of Sarcolysin-NP — 8,4 mg/kg), which was higher in comparison with free substance by more than 24% and 17%, respectively. Differences in the life span of the treated animals were revealed significantly at a dose of 10 mg/kg and amounted to 25% and 17,4% for lymphocytic leukemia P388 and L1210, respectively, and 11% for adenocarcinoma Ca755. In an experiment on rats, acute toxicity of Sarcolysin-NP administered intravenously showed that an average LD50 value 2-3 times exceeded a similar parameter for commercial preparations of free sarcolysin (Melphalan and Alkeran), which indicates its lower toxicity.

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In Silico, In Vitro, and In Vivo Antitumor and Anti-Inflammatory Evaluation of a Standardized Alkaloid-Enriched Fraction Obtained from Boehmeria caudata Sw. Aerial Parts

Molecules ◽

10.3390/molecules25174018 ◽

2020 ◽

Vol 25 (17) ◽

pp. 4018

Author(s):

Paula P. de Paiva ◽

Julia H. B. Nunes ◽

Fabiana R. Nonato ◽

Ana L. T. G. Ruiz ◽

Rafael R. T. Zafred ◽

...

Keyword(s):

Human Tumor ◽

Antitumor Agent ◽

Docking Studies ◽

In Vivo Studies ◽

Myeloperoxidase Activity ◽

Aerial Parts ◽

M Phase ◽

Anti Inflammatory

In the context of the cancer-inflammation relationship and the use of natural products as potential antitumor and anti-inflammatory agents, the alkaloid-enriched fraction of Boehmeriacaudata (BcAEF) aerial parts was evaluated. In vitro antiproliferative studies with human tumor cell lines showed high activity at low concentrations. Further investigation on NCI-H460 cells showed an irreversible effect on cell proliferation, with cell cycle arrest at G2/M phase and programmed cell death induction. Molecular docking studies of four alkaloids identified in BcAEF with colchicine’s binding site on β-tubulin were performed, suggesting (−)-C (15R)-hydroxycryptopleurine as the main inductor of the observed mitotic death. In vivo studies showed that BcAEF was able to reduce Ehrlich tumor volume progression by 30 to 40%. Checking myeloperoxidase activity, BcAEF reduced neutrophils migration towards the tumor. The in vivo anti-inflammatory activity was evaluated by chemically induced edema models. In croton oil-induced ear edema and carrageenan (CG)-induced paw edema models, BcAEF reduced edema around 70 to 80% together with inhibition of activation and/or migration of neutrophils to the inflammatory area. All together the results presented herein show BcAEF as a potent antitumor agent combining antiproliferative and anti-inflammatory properties, which could be further explored in (pre)clinical studies.

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P12.01 Local implantation of thermoresponsive interferon alpha-polypeptide conjugate combined with temozolomide for post-surgical glioblastoma chemoimmunotherapy

Neuro-Oncology ◽

10.1093/neuonc/noz126.212 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii59-iii59

Author(s):

P Liang ◽

W Zhuoran ◽

G Weiping ◽

W Guihuai

Keyword(s):

Release Kinetics ◽

Physicochemical Characterization ◽

Antitumor Agent ◽

Genetically Engineered ◽

Resection Cavity ◽

Post Surgery ◽

Zero Order Release ◽

Immunosuppressive Microenvironment

Abstract BACKGROUND Glioblastoma(GBM) is associated with gloomy prognosis despite maximal safe resection and following chemoradiation. In recent years, significant progress has been made in cancer immunotherapy except for GBM, which is largerly due to its local immunosuppressive microenvironment. Some research has demonstrated that local immunotherapy may be more efficient than systematic administrators. IFNα has been investigated as antitumor agent for some cancers, including glioma. Nevertheless, the short circulating half-life greatly limits its clinical application. Hence, a thermoresponsive IFNα-elastin-like polypeptide (IFNα-ELP) was genetically engineered for the earliest local intervention post-surgery. MATERIAL AND METHODS Firstly, IFNα-ELP(V) was constructed, expressed and purified, then, its physicochemical characterization was verified. The tumor was resected 10 days after U87MG-mCherry-luc cells orthotopic implantation, and IFNα-ELP(V) was injected into the resection cavity. Two days later, temozolomide(TMZ) was intraperitoneally injected. Using in vivo imaging technique, we could monitor the trends in tumor size. The survival time of mice was counted. Biosafety was evaluated by peripheral blood biochemistry analysis and pathology of the organs. RESULTS In this study, the bioconjugate not only in situ deposited in the resection cavity because of the thermoresponsive characteristic, but also showed zero-order release kinetics from the depot and dramatically improved pharmacokinetics and biodistribution of IFNα. Consequently, it showed the inhibition of tumor relapse in GBM orthotopic resection mice models. When followed by TMZ intraperitoneal injection, IFNα-ELP(V) could significantly prevent the tumor recurrence than itself or TMZ alone. Biosafety results indicated that the systemic toxicity of IFNα-ELP(V) in mice can be reduced to safe levels. CONCLUSION The results reveal that local implantation of thermoresponsive IFNα-ELP(V) combined with TMZ exhibits the synergy of post-surgical GBM chemoimmunotherapy.

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Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells

Blood ◽

10.1182/blood-2009-10-248245 ◽

2010 ◽

Vol 116 (19) ◽

pp. 3887-3898 ◽

Cited By ~ 37

Author(s):

Claudia Cocco ◽

Sara Canale ◽

Chiara Frasson ◽

Emma Di Carlo ◽

Emanuela Ognio ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Antitumor Activity ◽

Molecular Mechanisms ◽

Lymphoblastic Leukemia ◽

Antitumor Agent ◽

Underlying Mechanisms ◽

Interleukin 23 ◽

Novel Drug

Abstract Interleukin (IL)–23 is a proinflammatory cytokine belonging to the IL-12 superfamily. The antitumor activity of IL-23 is controversial, and it is unknown whether or not the cytokine can act directly on tumor cells. The aim of this study was to investigate the potential direct antitumor activity of IL-23 in pediatric B-acute lymphoblastic leukemia (B-ALL) cells and to unravel the molecular mechanisms involved. Here, we show, for the first time, that IL-23R is up-regulated in primary B-ALL cells, compared with normal early B lymphocytes, and that IL-23 dampens directly tumor growth in vitro and in vivo through the inhibition of tumor cell proliferation and induction of apoptosis. The latter finding is related to IL-23–induced up-regulation of miR15a expression and the consequent down-regulation of BCL-2 protein expression in pediatric B-ALL cells. This study demonstrates that IL-23 possesses antileukemic activity and unravels the underlying mechanisms. Thus, IL-23 may be a candidate novel drug for the treatment of B-ALL patients unresponsive to current therapeutic standards.

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Salinomycin suppresses tumorigenicity of liver cancer stem cells and Wnt/beta-catenin signaling

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200123121225 ◽

2020 ◽

Vol 15 ◽

Cited By ~ 1

Author(s):

Qiuping Liu ◽

Jinghui Sun ◽

Qing Luo ◽

Yang Ju ◽

Guanbin Song

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Liver Cancer ◽

Signaling Pathway ◽

Chemotherapy Resistance ◽

Antitumor Agent ◽

Beta Catenin ◽

Liver Cancer Stem Cells

Background: Accumulating evidence has revealed the important role of cancer stem cells (CSCs) in driving tumor initiation and tumor relapse or metastasis. Therapeutic strategies that selectively target CSCs may be effective approaches to eliminate cancer. Salinomycin, an antitumor agent, was identified as a selective inhibitor of several types of CSCs. We previously reported that salinomycin inhibits the migration and invasiveness of liver cancer stem cells (LCSCs). Objective: This study was conducted to explore the role of salinomycin in supressing stemness properties of LCSCs and the mechanism. Methods: LCSCs were identified and enriched from MHCC97H cells. Salinomycin was used to treat LCSCs at the indicated concentrations. Sphere formation ability, chemotherapy resistance, expression of CSC surface markers, Young's modulus and tumorigenicity of LCSCs were assessed to evaluate the effect of salionmycin on LCSCs. The expression of β-catenin was evaluated by western blotting. LiCl was used to activate the Wnt/β-catenin signaling pathway. Results: Salinomycin suppresses the stemness properties of LCSCs. Moreover, salinomycin could also inhibit the activation of Wnt/β-catenin signaling in LCSCs. Nevertheless, the stemness properties of LCSCs could be recovered when Wnt/β-catenin signaling was activated by LiCl. Further studies demonstrated that salinomycin also significantly reduces the tumorigenicity of LCSCs in vivo by suppressing the Wnt/β-catenin signaling pathway. Conclusion: Salinomycin could suppress stemness properties and induce differentiation of LCSCs through the Wnt/β-catenin signaling pathway, which provides evidence that salinomycin may serve as a potential drug for liver cancer therapy targeting LCSCs in the clinic.

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