Multiple pathways were involved in tubeimoside-1-induced cytotoxicity of HeLa cells

J Proteomics. 2011 Dec 21;75(2):491-501. doi: 10.1016/j.jprot.2011.08.014. Epub 2011 Aug 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • CDC2 Protein Kinase / antagonists & inhibitors
  • Calcium Signaling / drug effects
  • Cell Cycle / drug effects
  • Cell Cycle Checkpoints / drug effects*
  • Checkpoint Kinase 2
  • Cucurbitaceae / chemistry
  • Cyclin B1 / antagonists & inhibitors
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Protein-Serine-Threonine Kinases / metabolism
  • Reactive Oxygen Species / metabolism
  • Saponins / pharmacology*
  • Triterpenes / pharmacology*
  • cdc25 Phosphatases / antagonists & inhibitors

Substances

  • Antineoplastic Agents, Phytogenic
  • Cyclin B1
  • Reactive Oxygen Species
  • Saponins
  • Triterpenes
  • tubeimoside I
  • Checkpoint Kinase 2
  • CHEK2 protein, human
  • Protein-Serine-Threonine Kinases
  • CDC2 Protein Kinase
  • CDC25C protein, human
  • cdc25 Phosphatases