Protein mass spectrometry reveals lycorine exerting anti-multiple-myeloma effect by acting on VDAC2 and causing mitochondrial abnormalities

Biotechnol Lett. 2021 Mar;43(3):537-546. doi: 10.1007/s10529-020-03053-2. Epub 2021 Jan 1.

Abstract

Objective: Two-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF mass spectrometry were performed to compare the proteomic alterations of lycorine-treated and control cells to further investigate the anti-multiple myeloma (MM) mechanisms of lycorine.

Results: Mass spectrometry results showed that after lycorine treatment of MM cells, 42% of the differentially expressed proteins had subcellular localization, mainly, on mitochondria. Voltage-dependent anion-selective channel protein 2 (VDAC2), the most abundant protein in the outer mitochondrial membrane, was up-regulated after treatment with lycorine and was subsequently verified by western blot analysis. Further studies on mitochondria found that lycorine was able to increase abnormal mitochondria and increase mitochondrial membrane potential.

Conclusions: Lycorine can achieve the effect of resisting multiple myeloma by acting on VDAC2 and causing mitochondrial abnormalities.

Keywords: 2-DE; Abnormal mitochondria; Lycorine; MALDI-TOF/TOF mass spectrometry; Multiple myeloma; VDAC2.

MeSH terms

  • Amaryllidaceae Alkaloids / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Electrophoresis, Gel, Two-Dimensional
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / pathology
  • Multiple Myeloma / metabolism*
  • Phenanthridines / pharmacology*
  • Proteome / analysis
  • Proteome / drug effects*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Voltage-Dependent Anion Channel 2 / metabolism*

Substances

  • Amaryllidaceae Alkaloids
  • Antineoplastic Agents
  • Phenanthridines
  • Proteome
  • VDAC2 protein, human
  • Voltage-Dependent Anion Channel 2
  • lycorine