Effect of Marsdenia tenacissima extract on G2/M cell cycle arrest by upregulating 14-3-3σ and downregulating c-myc in vitro and in vivo / 中草药·英文版

Objective: Marsdenia tenacissima extract (MTE) is a traditional Chinese herbal medicine with anti-cancer activity. In some previous studies, different mechanism actions of the anti-cancer effect of MTE have been revealed. In this study, we first observed that MTE exhibited G2/M cell cycle arrest on two different human breast cancer cell lines, MDA-MB-231 and MCF-7 by mediating 14-3-3σ and c-myc. Methods: The effect of MTE on G2/M cell cycle arrest was evaluated in MDA-MB-231 and MCF-7 cell lines. MTT assay was done for evaluation of cell viability. Flow cytometry was employed for cell cycle analysis. Western blotting analysis and immunohistochemistry were performed to analyze the expression of G2/M cell cycle-related key protein in cells and tissue samples. Animal studies have been conducted to elucidate the anti-tumor effect of MTE. Results: Cell cycle is the backbone for developing cancer. Cell cycle proteins play a major role in the progression of cell cycle and cell proliferation. However, some key protein directly or indirectly modulate the action of cell cycle protein that highly affect cell cycle regulation. In order to investigate cellular proliferation of cancer, we observed that MTE induced the upregulation of 14-3-3σ and downregulation of c-myc, and then reduced the expression of G2/M cell cycle associated key protein, leading to the inhibition of cellular entry into mitosis phase. We also confirmed that MTE exerted a significant antitumor effect on the MDA-MB-231 xenograft model in vivo. Conclusion: G2/M cell cycle arrest occurred by the action of MTE, mediated by the upregulation of 14-3-3σ as well as downregulation of c-myc in MDA-MB-231 and MCF-7 cell lines.

Marsdenia tenacissima extract alters crucial metabolites in cancer, determined by 1 H NMR based metabolomics approach

ABSTRACT Altered metabolites level in the biosystems, is the potential cause of cancer, the primary reason of alteration of metabolism is change in nutrient consumption and waste excretion, as a result genetic mutation leads to cancer initiation and progression. Aberration of specific metabolites such as fumarate, succinate, 2-hydroxyglutarate may alter cell signaling. We collected liver and kidney samples and prepared for 1H NMR analysis, then executed NMR spectroscopy. We used a set of domestic R scripts to perform an unsupervised principal component analysis (PCA) and a supervised orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA). It signifies class discrimination for getting a clear separation, whereas PCA scores plot signifies the model group kept further away from the control group than drug group on the horizontal axis. In another PCA scores plots, most parts of the control group was overlapping with the drug group but was distant from the model group. Marsdenia tenacissima extract (MTE) (Chines name: Xiao-Ai-Ping, XAP) modulates level of crucial metabolites such as fumarate, lactate, succinate, determined by 1H NMR spectroscopy and their altered level contributes major role in cancer

Marsdenia tenacissima extract induces G0/G1 cell cycle arrest in human esophageal carcinoma cells by inhibiting mitogen-activated protein kinase (MAPK) signaling pathway / 中国天然药物

Marsdenia tenacissima extract (MTE, trade name: Xiao-Ai-Ping injection) is an extract of a single Chinese plant medicine. It has been used for the treatment of cancer in China for decades, especially for esophageal cancer and other cancers in the digestive tract. In the present study, the potential mechanism for MTE's activity in esophageal cancer was explored. The effects of MTE on the proliferation of human esophageal cancer cells (KYSE150 and Eca-109) were investigated by the MTT assay, the BrdU (bromodeoxyuridine) incorporation immunofluorescence assay, and flow cytometric analysis. MTE inhibited cell proliferation through inducing G0/G1 cell cycle arrest in KYSE150 and Eca-109. Western blot analysis was employed to determine protein levels in the MTE treated cells. Compared with the control cells, the expression levels of the cell cycle regulatory proteins cyclin D1/D2/D3, cyclin E1, CDK2/4/6 (CDK: cyclin dependent kinase), and p-Rb were decreased significantly in the cells treated with MTE at 40 mg·mL(-1). In addition, MTE had an inhibitory effect on the MAPK (mitogen-activated protein kinase) signal transduction pathway, including ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase), and p38MAPK. Moreover, MTE showed little additional effects on the regulation of cyclin D1/D3, CDK4/6, and p-Rb when the ERK pathway was already inhibited by the specific ERK inhibitor U0126. In conclusion, these data suggest that MTE inhibits human esophageal cancer cell proliferation through regulation of cell cycle regulatory proteins and the MAPK signaling pathways, which is probably mediated by the inhibition of ERK activation.

Stability of Chlorogenic Acid in Marsdenia Tenacissima Extract / 中国药房

OBJECTIVE:To study the factors influencing the stability of Chlorogenic acid in Marsdenia tenacissima extract.METHODS:The contents of Chlorogenic acid in Marsdenia tenacissima extract in different solvents,different lighting and different time under the heat were determined by HPLC.RESULTS:The Chlorogenic acid in Marsdenia tenacissima extract in organic solvents was more stable,in addition,lighting and heating temperature were important factors affecting the stability of the Chlorogenic acid.CONCLUSION:The stability of the Chlorogenic acid in Marsdenia tenacissima extract changes in different conditions;and the study results serve as a reference for the preparation,storage,analysis and production of Marsdenia tenacissima extract.