Effects of brucine on bone metabolism in multiple myeloma

Mol Med Rep. 2012 Aug;6(2):367-70. doi: 10.3892/mmr.2012.920. Epub 2012 May 17.

Abstract

The aim of this study was to explore the effects of brucine on bone metabolism in multiple myeloma (MM) and to compare brucine and bortezomib regarding the effects on MM in vitro. The half maximal inhibitory concentration (IC50) values of brucine and bortezomib in the MM cell line U266 were detected by MTT assay. In addition, the expression of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG) and osteoprotegerin ligand (also termed receptor activator of nuclear factor κB ligand) (RANKL) at mRNA levels were measured by RT-PCR. IC50 of bortezomib in the U266 cell line at 48 h was 22.4 nmol/l, and that of brucine was 0.16 nmol/l. Compared with osteoblasts incubated with MM cell supernatant alone, the mRNA levels of ALP, OC and OPG in osteoblasts co-treated with brucine and MM cell supernatant were higher (p<0.05), while the mRNA expression of RANKL was lower, and the ranges of the changes were all larger than those of the group treated with bortezomib (P<0.05). Brucine exerts effects on bone metabolism in multiple myeloma through the regulation of osteoclasts by osteoblasts.

Keywords: brucine; multiple myeloma; osteoblast; osteoclast.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Antineoplastic Combined Chemotherapy Protocols
  • Apoptosis
  • Bone and Bones / drug effects*
  • Bone and Bones / metabolism*
  • Boronic Acids / pharmacology
  • Bortezomib
  • Cell Differentiation
  • Cell Line, Tumor
  • Culture Media / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology*
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Osteoprotegerin / genetics
  • Osteoprotegerin / metabolism
  • Polymerase Chain Reaction / methods
  • Pyrazines / pharmacology
  • RANK Ligand / genetics
  • RANK Ligand / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Stem Cells / pathology*
  • Strychnine / analogs & derivatives*
  • Strychnine / pharmacology

Substances

  • Boronic Acids
  • Culture Media
  • Osteoprotegerin
  • Pyrazines
  • RANK Ligand
  • RNA, Messenger
  • RNA, Neoplasm
  • TNFSF11 protein, human
  • Osteocalcin
  • Bortezomib
  • brucine
  • Alkaline Phosphatase
  • Strychnine