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Sesquiterpene lactones derived from Saussurea lappa induce apoptosis and inhibit invasion and migration in neuroblastoma cells.

Abstract
Neuroblastoma is among the most fatal of solid tumors in the pediatric age group, even when treated aggressively. Therefore, a new effective therapeutic drug(s) for neuroblastoma is urgently needed. To clarify the anticancer effects of the sesquiterpene lactones dehydrocostus lactone and costunolide, derived from Saussurea lappa, we examined the cytotoxic and migration/invasion-inhibitory effects of these compounds against neuroblastoma cell lines. Both the compounds exerted significant cytotoxicity against the neuroblastoma cell lines IMR-32, NB-39, SK-N-SH, and LA-N-1. Evidence of cellular apoptosis, such as nuclear condensation and membrane inversion, were observed after treatment with these compounds. Both compounds induced caspase-7 activation and PARP cleavage as confirmed by Western blotting. Furthermore, the sesquiterpene lactones also suppressed invasion and migration of the neuroblastoma cells. These results suggest that dehydrocostus lactone and costunolide are promising candidates for being developed into novel anticancer drugs effective against neuroblastoma.
AuthorsKeiichi Tabata, Yuki Nishimura, Taiji Takeda, Masahiro Kurita, Taketo Uchiyama, Takashi Suzuki
JournalJournal of pharmacological sciences (J Pharmacol Sci) Vol. 127 Issue 4 Pg. 397-403 (Apr 2015) ISSN: 1347-8648 [Electronic] Japan
PMID25953266 (Publication Type: Journal Article)
CopyrightCopyright © 2015 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Benzazepines
  • Lactones
  • Sesquiterpenes
  • mozavaptan
  • dehydrocostus lactone
  • costunolide
  • Caspase 7
Topics
  • Antineoplastic Agents, Phytogenic
  • Apoptosis (drug effects)
  • Benzazepines
  • Caspase 7 (metabolism)
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Drug Design
  • Humans
  • Lactones (pharmacology, therapeutic use)
  • Neoplasm Invasiveness (pathology)
  • Neuroblastoma (drug therapy, enzymology, pathology)
  • Saussurea (chemistry)
  • Sesquiterpenes (pharmacology, therapeutic use)

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