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Structural Characterization and Anti-Proliferation Activities Against Tumor Cells of an Arabinogalactan from Juniperus convallium.

ABSTRACT: As a hyperproliferative disorder, cancer has continued to be a major public health challenge. In the present study, a polysaccharide JC-PS1 was isolated and purified from Juniperus convallium. JC-PS1 is a heteropolysaccharide composed of Ara, Gal, GalA and Rha with the average molecular weight of 280 kDa. Based on the methylation and 2D NMR analysis, JC-PS1 was elucidated as a backbone of ?5)-?-Araf-(1? and ?3,5)-?-Araf-(1?, and three kinds of branches attached to the O-3 position of ?3,5)-?-Araf-(1?, including ?-GalpA-(1?3)-?-Galp-(1?, ?-Araf-(1?3)-?-Rhap-(1? and ?-Araf-(1?3)-?-Galp-(1?. Accordingly, the atomic force microscopy of JC-PS1 showed a linear filamentous structure with small proportion of branches. Furthermore, JC-PS1 exhibited significant anti-proliferation activities against PANC-1, A431, MDA-MB-231, U118MG and H1975 cells with the IC₅₀ values of 296.8, 477.9, 657.4, 686.7 and 862.1 ?g/mL, respectively. This indicated that JC-PS1 could be a potential therapeutic agent for the treatment of cancer.

SUBMITTER: Li B

PROVIDER: S-EPMC6571648 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Structural Characterization and Anti-Proliferation Activities Against Tumor Cells of an Arabinogalactan from Juniperus convallium.

Li Beibei B Dong Mengxue M De Ji J Ye Li L Chen Daofeng D Lu Yan Y

Molecules (Basel, Switzerland) 20190514 10

As a hyperproliferative disorder, cancer has continued to be a major public health challenge. In the present study, a polysaccharide JC-PS1 was isolated and purified from Juniperus convallium. JC-PS1 is a heteropolysaccharide composed of Ara, Gal, GalA and Rha with the average molecular weight of 280 kDa. Based on the methylation and 2D NMR analysis, JC-PS1 was elucidated as a backbone of →5)-α-Araf-(1→ and →3,5)-α-Araf-(1→, and three kinds of branches attached to the O-3 po ...[more]

PMID: 31091760

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Project description:BackgroundTo identify a novel therapeutic agent for hepatocellular carcinoma (HCC), for which no promising therapeutic agent exists, we screened a panel of plants and found that Juniperus chinensis exhibited potential antiangiogenic and anti-HCC activities. We further investigated the antiangiogenic and anti-HCC effects of the active ingredient of J. chinensis extract, CBT-143-S-F6F7, both in vitro and in vivo.MethodsA tube formation assay conducted using human umbilical vein endothelial cells (HUVECs) was first performed to identify the active ingredient of CBT-143-S-F6F7. A series of angiogenesis studies, including HUVEC migration, Matrigel plug, and chorioallantoic membrane (CAM) assays, were then performed to confirm the effects of CBT-143-S-F6F7 on angiogenesis. The effects of CBT-143-S-F6F7 on tumor growth were investigated using a subcutaneous and orthotopic mouse model of HCC. In vitro studies were performed to investigate the effects of CBT-143-S-F6F7 on the cell cycle and apoptosis in HCC cells. Moreover, protein arrays for angiogenesis and apoptosis were used to discover biomarkers that may be influenced by CBT-143-S-F6F7. Finally, nuclear magnetic resonance analysis was conducted to identify the compounds of CBT-143-S-F6F7.ResultsCBT-143-S-F6F7 showed significantly antiangiogenic activity in various assays, including HUVEC tube formation and migration, CAM, and Matrigel plug assays. In in vivo studies, gavage with CBT-143-S-F6F7 significantly repressed subcutaneous Huh7 tumor growth in severe combined immunodeficient (SCID) mice, and prolonged the survival of orthotopic Huh7 tumor-bearing SCID mice (a 40 % increase in median survival duration compared with the vehicle-treated mice). Immunohistochemical staining of subcutaneous Huh7 tumors in CBT-143-S-F6F7-treated mice showed a significantly decrease in the cell cycle regulatory protein cyclin D1, cellular proliferation marker Ki-67, and endothelial marker CD31. CBT-143-S-F6F7 caused arrest of the G2/M phase and induced Huh7 cell apoptosis, possibly contributing to the inhibition of HCC tumors. Protein array analysis revealed that several angiogenic and antiapoptotic factors were suppressed in CBT-143-S-F6F7-treated Huh7 cells. Finally, five compounds from CBT-143-S-F6F7 were identified.ConclusionsAccording to these results, we report for the first time the antiangiogenic and anti-HCC activities of CBT-143-S-F6F7, the active fractional extract of J. chinensis. We believe that CBT-143-S-F6F7 warrants further evaluation as a new anti-HCC drug.

Dataset Information

Structural Characterization and Anti-Proliferation Activities Against Tumor Cells of an Arabinogalactan from Juniperus convallium.

Publications

Structural Characterization and Anti-Proliferation Activities Against Tumor Cells of an Arabinogalactan from <i>Juniperus convallium</i>.

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