A novel synthetic drug, LB-18, closely related to lembehyne-A derived from a marine sponge, induces caspase-independent cell death to human neuroblastoma cells

Int J Oncol. 2006 Jul;29(1):169-73.


Neuroblastoma is a common solid tumor of children that arises from the sympathetic nervous system. Much work has consequently focused on the possibility of inducing marked cell death in neuroblastoma, and the new effective drugs are required. We have newly synthesized LB-18, closely related to lembehyne A (LB-A), a polyacetylene derived from a kind of marine sponge. LB-A has been shown to induce p21/WAF1 and causes G1 phase arrest in mouse neuroblastoma Neuro2A cells; however, we show here that LB-18 causes cell death in human neuroblastoma KP-N-TK cells in a dose-dependent manner. TUNEL assay and flow cytometric analysis showed that the cell death caused by LB-18 was associated with the DNA damage but the pan-caspase inhibitor, zVAD-fmk, could not prevent the cell death. Western blot analysis and cleavage of the caspase-3 or -7 substrate assay showed that LB-18 could not activate caspases 3, 7, 8 and 9. These results suggest that LB-18 causes caspase-independent cell death in human neuroblastoma cells. In the future, LB-18 may be useful for cancer therapeutics, especially for neuroblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemical synthesis
  • Alkynes / chemistry*
  • Alkynes / isolation & purification
  • Alkynes / pharmacology*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Fatty Alcohols / chemical synthesis
  • Fatty Alcohols / chemistry*
  • Fatty Alcohols / isolation & purification
  • Fatty Alcohols / pharmacology*
  • Haliclona / chemistry*
  • Humans
  • Molecular Structure
  • Neuroblastoma / enzymology
  • Neuroblastoma / pathology
  • Time Factors


  • Alkynes
  • Antineoplastic Agents
  • Fatty Alcohols
  • LB-18 compound
  • lembehyne A
  • Caspases