title: Syringolin A, a new plant elicitor from the phytopathogenic bacterium Pseudomonas syringae pv. syringae, inhibits the proliferation of neuroblastoma and ovarian cancer cells and induces apoptosis.
abstract: Syringolin A is a new plant elicitor produced by the plant pathogen Pseudomonas syringae pv. syringae. The goal of this study was to investigate whether syringolin A exhibits anti-proliferative properties in cancer cells. The treatment of human neuroblastoma (NB) cells (SK-N-SH and LAN-1) and human ovarian cancer cells (SKOV3) with syringolin A (0-100 microm) inhibited cell proliferation in a dose-dependent manner. The IC(50) (50% inhibition) for each cell line ranged between 20 microm and 25 microm. In SK-N-SH cells, the treatment with 20 microm syringolin A led to a rapid (24 h) increase of the apoptosis-associated tumour suppressor protein p53. In addition, we found that the treatment of SK-N-SH cells caused severe morphological changes after 48 h such as rounding of cells and loss of adherence, both conditions observed during apoptosis. The induction of apoptosis by syringolin A was confirmed by both poly (ADP-ribose) polymerase (PARP) cleavage and annexin V assay. Taken together, we show for the first time that the natural product syringolin A exhibits anti-proliferative activity and induces apoptosis. Syringolin A and structurally modified syringolin A derivatives may serve as new lead compounds for the development of novel anticancer drugs.
authors.affiliation: Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Coleman
authors.forename: J P
authors.initials: JP
authors.lastname: Rocetes
authors.forename: D J
authors.initials: DJ
authors.lastname: Park
authors.forename: C J
authors.initials: CJ
authors.lastname: Wallick
authors.forename: B J
authors.initials: BJ
authors.lastname: Warn-Cramer
authors.forename: K
authors.initials: K
authors.lastname: Michel
authors.forename: R
authors.initials: R
authors.lastname: Dudler
authors.forename: A S
authors.initials: AS
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D009423:Nervous System Neoplasms / Q000473:pathology*; D009447:Neuroblastoma / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D044224:Pseudomonas syringae / Q000737:chemistry; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D016159:Tumor Suppressor Protein p53; C407267:syringolin A; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3