title: 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.
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tabata
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Takeda
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurita
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Uchiyama
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan; School of Medicine, Nihon University, 30-1 Oyaguchikami-cho, Itabashi-ku, Tokyo 173-0032, Japan. Electronic address: suzuki.takashi85@nihon-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects*; D001552:Benzazepines; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015195:Drug Design; D006801:Humans; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009447:Neuroblastoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D030441:Saussurea / Q000737:chemistry*; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001552:Benzazepines; D007783:Lactones; D012717:Sesquiterpenes; C076251:mozavaptan; C083030:dehydrocostus lactone; C002602:costunolide; D053179:Caspase 7
keywords: Apoptosis; Invasion; Migration; Neuroblastoma; Sesquiterpenes