Capilliposide C Sensitizes Esophageal Squamous Carcinoma Cells to Oxaliplatin by Inducing Apoptosis Through the PI3K/Akt/mTOR Pathway.[Pubmed: 28463955]

BACKGROUND Although platinum-based chemotherapy is the most effective strategy for esophageal cancer, toxicity and drug resistance limit the dose administration and the application of chemotherapy. Capilliposide C (CPS-C) is isolated from the Chinese herb Lysimachia capillipes Hemsl and is approved to be effective against carcinomas. However, the activity of CPS-C against esophageal cancer remains unclear. The present study was conducted to assess the chemosensitizing effects of CPS-C for enhancing the therapeutic efficacy of oxaliplatin in esophageal squamous carcinoma cells and explore the underlying mechanism. MATERIAL AND METHODS Human esophageal squamous cell carcinoma (ESCC) TE-1 and TE-2 were used. Several in vitro and in vivo analyses were carried out, including MTT, Annexin V/PI, Western blot, and TUNEL and immunohistochemistry in a xenograft model. RESULTS CPS-C significantly enhanced the proliferative inhibition and apoptotic effect of oxaliplatin in ESCC cells. Oxaliplatin combined with CPS-C decreased the expressions of PI3K, phospho-Akt, phospho-mTOR, Bcl-2, and Bcl-XL, and increased the expression of Bax and caspase-3 significantly compared to oxaliplatin-only treatment. Furthermore, in the ESCC xenograft model, CPS-C significantly enhanced the anti-cancer effects and apoptosis of oxaliplatin. CONCLUSIONS The results indicated that CPS-C enhanced the anti-proliferative and apoptotic effect of oxaliplatin by modulating the PI3K/Akt/mTOR pathway on ESCC in vitro and in vivo.

Tissue distribution of capilliposide B, capilliposide C and their bioactive metabolite in mice using liquid -tandem mass spectrometry.[Pubmed: 27859436]

Lysimachia capillipes Hemsl (Primulaceae), a folk medicinal plant in China, showed significant anti-tumor activities in vivo and in vitro. Capilliposide B (LC-B) and capilliposide C (LC-C) are the main bioactive components in this plant. To explore their tissue distribution, a reliable bioanalytical method for the quantification of LC-B, LC-C and their bioactive metabolite, capilliposide A (LC-A), in mouse tissues was developed and validated. In this study, the tissue distribution profiles of the three compounds were examined after intravenous administration of pure LC-B and oral administration of total saponins of L. capillipes Hemsl extract (LCE) for 10 days. Method validation was conducted over the curve range 10.0-5000 ng/mL for all three analytes in various tissue homogenates. The relative standard deviation of intra-day and inter-day precision of the QC samples was <14.7%, and the accuracy ranged from 85.9 to 114.0%. The results indicated that LC-B was rapidly and widely distributed throughout the whole body except for muscle following intravenous administration of LC-B. In addition, LC-A was only in liver, intestine, lung and stomach. After oral administration of LCE, LC-B and LC-C were distributed into various tissues. The highest levels were observed in stomach and intestine.

Capilliposide from Lysimachia capillipes inhibits AKT activation and restores gefitinib sensitivity in human non-small cell lung cancer cells with acquired gefitinib resistance.[Pubmed: 27840409]

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Optimization of solid-phase extraction and liquid chromatography-tandem mass spectrometry for simultaneous determination of capilliposide B and its active metabolite in rat urine and feces: Overcoming nonspecific binding.[Pubmed: 27521984]

Capilliposide B, a novel oleanane triterpenoid saponin isolated from Lysimachia capillipes Hemsl, showed significant anti-tumor activities in recent studies. To characterize the excretion of Capilliposide B, a reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of Capilliposide B and its active metabolite, Capilliposide A in rat urine and feces. Sample preparation using a solid-phase extraction procedure was optimized by acidification of samples at various degrees, providing extensive sample clean-up with a high extraction recovery. In addition, rat urinary samples were pretreated with CHAPS, an anti-adsorptive agent, for overcoming nonspecific analytes adsorption during sample storage and process. The method validation was conducted over the curve range of 10.0-5000ng/ml for both analytes. The intra- and inter-day precision and accuracy of the QC samples showed ≤11.0% RSD and -10.4-12.8% relative error. The method was successfully applied to an excretion study of Capilliposide B following intravenous administration.

Capilliposide C derived from Lysimachia capillipes Hemsl inhibits growth of human prostate cancer PC3 cells by targeting caspase and MAPK pathways.[Pubmed: 24554216]

Prostate cancer, a common malignant tumor of the genitourinary system among elderly males, is difficult to cure. Capilliposide C (CPS-C) is a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl. Although CPS-C had been investigated in gastric cancer BGC-823 cells, prostate cancer PC3 cells, and ovarian cancer SK-OV-3 cells in nude mice in a dose-dependent manner without overt toxicity, its mechanism in the cancer cells has not been further studied. In the current study, PC3-cell-line-based in vitro models were used to explore the anti-cancer effect and mechanism of CPS-C. The results of cell viability assays showed that CPS-C exhibited dose- and time-dependent cytotoxicity against the prostate cancer cell lines PC3 and DU145. Observations using optical and electron microscope suggested the cytotoxicity of CPS-C. CPS-C-induced apoptosis was confirmed by the activation of caspases, down-regulation of Bcl-2, JNK, and P38α/β, and up-regulation of Bax, p-JNK, and p-P38. Results showed that CPS-C exhibits high toxicity toward two prostate cancer cells in vitro. Therefore, CPS-C may have great potential in the prevention and treatment of human prostate cancers.

Capilliposide Isolated from Lysimachia capillipes Hemsl. Induces ROS Generation, Cell Cycle Arrest, and Apoptosis in Human Nonsmall Cell Lung Cancer Cell Lines.[Pubmed: 24523821]

Several data has reported that capilliposide, extracted from a traditional Chinese medicine, Lysimachia capillipes Hemsl. (LC) could exhibit inhibitory effect on cell proliferation in various cancers. The current study investigated the antitumor efficacy of Capilliposide and elucidated its potential molecular mechanism involved in vivo and vitro. Our results indicated that LC capilliposide inhibited proliferation of lung cancer cells in a dose-dependent manner. LC capilliposide induced cell cycle arrest at the S stage and enhanced apoptosis in NSCLC cells. Treatment with LC capilliposide increased the intracellular level of ROS, which activated the mitochondrial apoptotic pathway. Blockage of ROS by NAC highly reversed the effect of LC capilliposide on apoptosis. Xenograft tumor growth was significantly lower in the LC-treated group compared with the untreated control group (P < 0.05). The results also show that LC treatment does not produce any overt signs of acute toxicity in vivo. These findings demonstrate that LC capilliposide could exert an anti-tumor effect on NSCLC through mitochondrial-mediated apoptotic pathway and the activation of ROS is involved.

Simultaneous determination of capilliposide B and capilliposide C in rat plasma by LC-MS/MS and its application to a PK study.[Pubmed: 24313264]

Lysimachia capillipes Hemsl (Primulaceae), a folk medicinal plant in China, showed significant anti-tumor activity in recent studies. A reliable LC-MS/MS method was developed and validated for the simultaneous determination of capilliposide B and capilliposide C, the major bioactive components in this plant, in rat plasma.

Isolation and characterization of two new saponins from Lysimachia capillipes.[Pubmed: 16870168]

Two new saponins, capilliposide K (1) and capilliposide L (2), were isolated from the whole plants of Lysimachia capillipes. Their structures were established by spectral and chemical techniques.

Two new triterpene saponins from Lysimachia capillipes.[Pubmed: 16864460]

Two new saponins, capilliposide G (1) and capilliposide H (2), were isolated from the whole plants of Lysimachia capillipes. Their structures were determined by 1D and 2D NMR, MS technique and chemical methods.

Three novel triterpenoid saponins from Lysimachia capillipes and their cytotoxic activities.[Pubmed: 16595968]

Three new saponins, capilliposide A (1), capilliposide B (2) and capilliposide C (3) were isolated from an ethanol extract of Lysimachia capillipes. Their structures were determined by 1D and 2D NMR (1H-1H COSY, HMBC, HMQC, DEPT and TOCSY) techniques, MS, and hydrolysis. Capilliposide B showed significant cytotoxicity against human A-2780 cells.