Pterostilbene Inhibits Human Multiple Myeloma Cells via ERK1/2 and JNK Pathway In Vitro and In Vivo

Int J Mol Sci. 2016 Nov 17;17(11):1927. doi: 10.3390/ijms17111927.

Abstract

Multiple myeloma (MM) is the second most common malignancy in the hematologic system, which is characterized by accumulation of plasma cells in bone marrow. Pterostilbene (PTE) is a natural dimethylated analog of resveratrol, which has anti-oxidant, anti-inflammatory and anti-tumor properties. In the present study, we examined the anti-tumor effect of PTE on MM cell lines both in vitro and in vivo using the cell counting kit (CCK)-8, apoptosis assays, cell cycle analysis, reactive oxygen species (ROS) generation, JC-1 mitochondrial membrane potential assay, Western blotting and tumor xenograft models. The results demonstrated that PTE induces apoptosis in the H929 cell line and causes cell cycle arrest at G0/G1 phase by enhancing ROS generation and reducing mitochondrial membrane potential. The anti-tumor effect of PTE may be caused by the activation of the extracellular regulated protein kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK) signaling pathways. Additionally, mice treated with PTE by intraperitoneal injection demonstrated reduced tumor volume. Taken together, the results of this study indicate that the anti-tumor effect of PTE on MM cells may provide a new therapeutic option for MM patients.

Keywords: ERK1/2; JNK; apoptosis; cell cycle; multiple myeloma; pterostilbene.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Damage
  • Female
  • G1 Phase Cell Cycle Checkpoints
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Membrane Potential, Mitochondrial / drug effects
  • Mice, Inbred NOD
  • Mice, SCID
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Reactive Oxygen Species / metabolism
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Stilbenes
  • pterostilbene