title: Marsdenia tenacissima extract induces G0/G1 cell cycle arrest in human esophageal carcinoma cells by inhibiting mitogen-activated protein kinase (MAPK) signaling pathway.
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.
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Complex Prescription of Traditional Chinese Medicine, School of Chinese Material Medicine, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jing-Qian
authors.initials: JQ
authors.lastname: Zhou
authors.affiliation: Nanjing Sanhome Pharmaceutical Co. Ltd., Nanjing 210038, China.
authors.forename: Cang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Nanjing Sanhome Pharmaceutical Co. Ltd., Nanjing 210038, China.
authors.forename: Song
authors.initials: S
authors.lastname: Qin
authors.affiliation: Nanjing Sanhome Pharmaceutical Co. Ltd., Nanjing 210038, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Nanjing Sanhome Pharmaceutical Co. Ltd., Nanjing 210038, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China. Electronic address: chaphalss@126.com.
authors.forename: Sen-Sen
authors.initials: SS
authors.lastname: Lin
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpuyuanst@126.com.
authors.forename: Sheng-Tao
authors.initials: ST
authors.lastname: Yuan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D031101:Marsdenia / Q000737:chemistry*
chemical_list: D004365:Drugs, Chinese Herbal; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cell cycle arrest; Human esophageal cancer; Marsdenia tenacissima extract; Mitogen-activated protein kinase signaling pathway