Marsdeniae tenacissimae extract (MTE) suppresses cell proliferation by attenuating VEGF/VEGFR2 interactions and promotes apoptosis through regulating PKC pathway in human umbilical vein endothelial cells.

Marsdeniae tenacissimae extract (MTE), commonly known as Xiao-Ai-Ping in China, is a traditional Chinese herb medicine capable of inhibiting proliferation and metastasis and boosting apoptosis in various cancer cells. However, little is known about the contribution of MTE towards tumor angiogenesis and the underlying mechanism. The present study aimed to evaluate the effects of MTE on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the molecular mechanism. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS) and PI-stained flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of HUVECs by arresting cell cycle at S phase (P < 0.05). Annexin V-FITC/PI-stained flow cytometry confirmed that MTE (160 μL·L-1) enhanced the apoptosis of HUVECs significantly (P < 0.001). Real-time quantitative RT-PCR and Western blot analyses showed an increase in Bax expression and a sharply decline in Bcl-2 expression; caspase-3 was activated simultaneously in a dose-dependent manner (P < 0.05). Further study observed the dose-dependent down-regulation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), P2Y6 receptor (P2Y6R), and chemokine (C-C motif) ligand 2 (CCL-2), along with the activation of PKC Δ and up-regulation of p53 in a dose-dependent manner in MTE-treated selected cells (P < 0.05). Collectively, the results from the present study suggested that MTE suppressed the proliferation by attenuating CCL-2-mediated VEGF/VEGFR2 interactions and promoted the apoptosis through PKCΔ-induced p53-dependent mitochondrial pathway in HUVECs, supporting that MTE may be developed as a potent anti-cancer medicine.

Chen BY ，Chen D ，Lyu JX ，Li KQ ，Jiang MM ，Zeng JJ ，He XJ ，Hao K ，Tao HQ ，Mou XZ ，Ying YM ，Zhang W ，Zhu MH ，Wang Z ... -  《-》

Marsdenia tenacissimae extraction (MTE) inhibits the proliferation and induces the apoptosis of human acute T cell leukemia cells through inactivating PI3K/AKT/mTOR signaling pathway via PTEN enhancement.

Wang Y ，Chen B ，Wang Z ，Zhang W ，Hao K ，Chen Y ，Li K ，Wang T ，Xie Y ，Huang Z ，Tong X ... -  《Oncotarget》

Marsdeniae tenacissima extract-induced growth inhibition and apoptosis in hepatoma carcinoma cells is mediated through the p53/nuclear factor-κB signaling pathway.

Wang Z ，Ying YM ，Li KQ ，Zhang Y ，Chen BY ，Zeng JJ ，He XJ ，Jiang MM ，Chen BX ，Wang Y ，Xu XD ，Hao K ，Zhu MH ，Zhang W ... -  《-》

Marsdenia Tenacissima Extract Inhibits Proliferation and Promotes Apoptosis in Human Ovarian Cancer Cells.

Zhang Y ，Zhang Y 《MEDICAL SCIENCE MONITOR》

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

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.

Fan W ，Sun L ，Zhou JQ ，Zhang C ，Qin S ，Tang Y ，Liu Y ，Lin SS ，Yuan ST ... -  《-》