title: Multiple pathways were involved in tubeimoside-1-induced cytotoxicity of HeLa cells.
abstract: The Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae) is a Chinese herb with anticancer potential. Its main active component tubeimoside-1 (TBMS1), a triterpenoid saponin, was previously proved as a potent anticancer chemotherapeutic agent; however, the molecular basis for its activities is still elusive. In the present study, subcellular proteomic study in the cytoplasm and membrane protein fractions extracted from HeLa cells revealed that proteins act as mediators of ROS generation and Ca(2+) regulation were substantially altered in expression upon TBMS1 stimuli. We also found that TBMS1 induced cell cycle arrest at G2/M phase accompanied by a decrease in G0/G1 phase in HeLa cells. Further biochemical studies showed that TBMS1 inhibited the levels of cyclinB1, Cdc2 and Cdc25C, but enhanced Chk2 phosphorylation. In addition, the cytoplasm sequestration of Cdc25C, Cip1/p21 induction and tubulin dyspolymerization also contributed to the TBMS1-mediated cell cycle arrest on the G2/M phase.
authors: School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361005, China.
authors: Yang
authors: Y
authors: Xu
authors: Yick-Pang
authors: YP
authors: Ching
authors: Yuan
authors: Y
authors: Zhou
authors: Jen-Fu
authors: JF
authors: Chiu
authors: Feng
authors: F
authors: Chen
authors: Qing-Yu
authors: QY
authors: He
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D020013:Calcium Signaling / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D064447:Checkpoint Kinase 2; D019662:Cucurbitaceae / Q000737:chemistry; D056744:Cyclin B1 / Q000037:antagonists & inhibitors; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D056744:Cyclin B1; D017382:Reactive Oxygen Species; D012503:Saponins; D014315:Triterpenes; C051084:tubeimoside I; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases