ABSTRACT
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.
Subject(s)
Humans , Apoptosis , Carcinoma , Drug Therapy , Cell Line, Tumor , Cell Proliferation , Drugs, Chinese Herbal , Pharmacology , Esophageal Neoplasms , Drug Therapy , Extracellular Signal-Regulated MAP Kinases , Metabolism , G1 Phase Cell Cycle Checkpoints , MAP Kinase Signaling System , Marsdenia , ChemistryABSTRACT
Epidermal growth factor receptor pathway substrate 8 (Eps8) is one of crucial kinase substrates for the epidermal growth factor receptors. Eps8 is related to mitosis and differentiation of normal cells. In recent years, it has been demonstrated that Eps8 involves in proliferation, metastasis and prognosis of many malignant tumors. Experiments have shown that Eps8 involves in Ras-Rac pathway of EGFR signaling by forming Eps8-Abi1-Sos1 tri-complex or participates in endocytosis mediated by rab5. Furthermore, Eps8 has also been found to regulate cell cycle. In conclusion, it may become a monitor and a new target for the treatment of malignant tumors. This review briefly introduces molecular structure and physiological function of Eps8, focusing on its function and molecular mechanism in proliferation, metastasis and prognosis of malignant tumors.