Experimental Therapy of Ovarian Cancer with Synthetic Makaluvamine Analog: In Vitro and In Vivo Anticancer Activity and Molecular Mechanisms of Action

Chen, Tao; Xu, Yi; Guo, Haijuan; Liu, Yanling; Hu, Pingting; Xia, Yang; Li, Xiaoguang; Ge, Shichao; Velu, Sadanandan E.; Nadkarni, Dwayaja H.; Wang, Wei; Zhang, Ruiwen; Wang, Hui

doi:10.1371/journal.pone.0020729

Cited by 34 publications

(33 citation statements)

References 33 publications

(49 reference statements)

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“…Live, early apoptotic, late apoptotic, and primary necrotic macrophages were characterized as Annexin V − PI − , Annexin V + PI − , Annexin V + PI + , or Annexin V − PI + using FACS analysis [25]. Live macrophages, early apoptotic, late apoptotic, and primary necrotic macrophages were characterized as Annexin V − PI − , Annexin V + PI − , Annexin V + PI + , or Annexin V + PI ++ using confocal microscopy [6].…”

Section: Fluorescence-activated Cell Sorter (Facs) Analysismentioning

confidence: 99%

PTX3 Is Located at the Membrane of Late Apoptotic Macrophages and Mediates the Phagocytosis of Macrophages

Guo

et al. 2011

J Clin Immunol

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Apoptotic macrophages are removed by neighboring phagocytes (efferocytosis), which is an important event in advanced atherosclerosis. Recent reports have elucidated some key molecular regulators in efferocytosis including complement C1q, MFGE8, and MERTK. However, it remains unknown whether the long pentraxin 3 (PTX3), which is an important molecule that is involved in apoptotic cell clearance in the immune response, plays a part in efferocytosis during advanced atherosclerosis. In this study, we modeled macrophage apoptosis in advanced plaques by incubating macrophages (peritoneal macrophages isolated from C57 mice) with free cholesterol (free cholesterol-induced apoptotic macrophages, FC-AMs). FC-AMs were added to a monolayer of fresh phagocytes to study the engulfment response. We observed that PTX3 was mainly located at the membrane of late apoptotic macrophages. The anti-PTX3 monoclonal Ab 16B5 inhibited the engulfment of late apoptotic macrophages by phagocytes in a dose-dependent manner (from 14.63% inhibition at 5 μg/ml to 26.19% inhibition at 50 μg/ml). These results suggest that PTX3 located at the membrane of late apoptotic macrophages mediates their phagocytosis by phagocytes in a cell model of advanced atherosclerosis.

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Section: Fluorescence-activated Cell Sorter (Facs) Analysismentioning

confidence: 99%

PTX3 Is Located at the Membrane of Late Apoptotic Macrophages and Mediates the Phagocytosis of Macrophages

Guo

et al. 2011

J Clin Immunol

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“…Because of their rich structural diversity and promising therapeutic applications, natural products and their derivatives have caught the attention of pharmacologists and chemists (18,19). We have been interested in developing new, effective, and safe drugs from natural products for cancer therapy (25,(46)(47)(48). Inula japonica Thunb is a traditional medicinal herb used for treatment of bronchitis, digestive disorders, diabetes, and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Japonicone A Suppresses Growth of Burkitt Lymphoma Cells through Its Effect on NF-κB

Xia

Liu

et al. 2013

Clinical Cancer Research

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Purpose: NF-kB, a transcriptional regulator of diverse genes involved in cell survival, proliferation, adhesion, and apoptosis, has been implicated in various malignancies. We discovered a potent natural NF-kB inhibitor, Japonicone A, from the traditional herb Inula japonica Thunb, evaluated its preclinical pharmacology and therapeutic activity, and investigated the underlying mechanisms of action for its antitumor activity.Experimental Design: Various types of cancer and normal cells were exposed to Japonicone A for cytotoxicity screening, followed by determination of cell apoptosis and cell-cycle arrest. Western blotting, immunostaining, and gene reporter assay were used to analyze NF-kB activity. Two xenograft models were used for therapeutic efficacy evaluation.Results: Japonicone A killed cancer cells but had low cytotoxicity to normal cells. Burkitt lymphoma cells were particularly sensitive. Japonicone A inhibited the growth and proliferation of Raji, BJAB, and NAMALWA lymphoma cells and resulted in G 2 -M phase arrest and apoptosis. Furthermore, exposure of cells to Japonicone A caused inactivation of the TNF-a-TAK1-IKK-NF-kB axis and inhibition of TNFa-stimulated NF-kB activity and nuclear translocation, followed by downregulation of NF-kB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP, TRAF2) and in the cell cycle and growth (cyclin D, c-Myc). Moreover, Japonicone A inhibited local growth and dissemination of cancer cells to multiple organs in vivo.Conclusion: Japonicone A exerts significant anticancer effects on Burkitt lymphoma cells in vitro and in vivo through targeting of the NF-kB signaling cascade. These results highlight the potential of Japonicone A as a chemotherapeutic agent and warrant its development as a therapy for lymphomas.

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“…Western Blotting experiments were carried out as reported (Chen et al, 2011). In Brief, HCC tumor tissues were homogenized in protein lysate buffer, and the debris was removed by centrifugation.…”

Section: Western Blottingmentioning

confidence: 99%

Asparagus Polysaccharide and Gum with Hepatic Artery Embolization Induces Tumor Growth and Inhibits Angiogenesis in an Orthotopic Hepatocellular Carcinoma Model

Weng

Xiang

Lin

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy.

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Experimental Therapy of Ovarian Cancer with Synthetic Makaluvamine Analog: In Vitro and In Vivo Anticancer Activity and Molecular Mechanisms of Action

Cited by 34 publications

References 33 publications

PTX3 Is Located at the Membrane of Late Apoptotic Macrophages and Mediates the Phagocytosis of Macrophages

PTX3 Is Located at the Membrane of Late Apoptotic Macrophages and Mediates the Phagocytosis of Macrophages

Japonicone A Suppresses Growth of Burkitt Lymphoma Cells through Its Effect on NF-κB

Asparagus Polysaccharide and Gum with Hepatic Artery Embolization Induces Tumor Growth and Inhibits Angiogenesis in an Orthotopic Hepatocellular Carcinoma Model

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