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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.

Abstract
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.
AuthorsMoriatsu Izumi, Shingo Yogosawa, Shunji Aoki, Hirotsuna Watanabe, Jun Kamiyama, Yoshinori Takahara, Yoshihiro Sowa, Motomasa Kobayashi, Hajime Hosoi, Tohru Sugimoto, Toshiyuki Sakai
JournalInternational journal of oncology (Int J Oncol) Vol. 29 Issue 1 Pg. 169-73 (Jul 2006) ISSN: 1019-6439 [Print] Greece
PMID16773197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Alkynes
  • Antineoplastic Agents
  • Fatty Alcohols
  • LB-18 compound
  • lembehyne A
  • Caspases
Topics
  • Alkynes (chemical synthesis, chemistry, isolation & purification, pharmacology)
  • Animals
  • Antineoplastic Agents (chemical synthesis, pharmacology)
  • Apoptosis
  • Caspases (metabolism)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Dose-Response Relationship, Drug
  • Fatty Alcohols (chemical synthesis, chemistry, isolation & purification, pharmacology)
  • Haliclona (chemistry)
  • Humans
  • Molecular Structure
  • Neuroblastoma (enzymology, pathology)
  • Time Factors

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