title: Lauroside B, a megastigmane glycoside from Laurus nobilis (bay laurel) leaves, induces apoptosis in human melanoma cell lines by inhibiting NF-κB activation.
abstract: Malignant melanoma is a highly aggressive tumor that frequently resists chemotherapy, so the search for new agents for its treatment is of great importance. In the present study, the antiproliferative propensity against human melanoma cell lines of lauroside B (1), a megastigmane glycoside isolated from Laurus nobilis (bay laurel) leaves, was investigated. This compound suppressed the proliferation of three human melanoma cell lines, namely, A375, WM115, and SK-Mel-28. The 1-induced inhibition of human melanoma cell proliferation was due to the induction of apoptosis, as demonstrated by FACS analysis with annexin V/PI staining and confirmed by activation of caspase-3 and by the cleavage of poly(ADP-ribose) polymerase (PARP). Growing evidence implicates NF-κB as an important contributor to metastasis and increased chemoresistance of melanoma. Thus, it was hypothesized that 1-induced apoptosis could be associated with suppression of NF-κB activation. The results showed that exposure of human melanoma cells to 1 inhibited IκB-α degradation and constitutive NF-κB DNA-binding activity as well as the expression, regulated by NF-κB, of two antiapoptotic genes, XIAP and c-FLIP. Induction of apoptosis by 1 in human aggressive melanoma cell lines has a potential high biological value.
authors.affiliation: Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Panza
authors.forename: Mariaroberta
authors.initials: M
authors.lastname: Tersigni
authors.forename: Maria
authors.initials: M
authors.lastname: Iorizzi
authors.forename: Franco
authors.initials: F
authors.lastname: Zollo
authors.forename: Simona
authors.initials: S
authors.lastname: De Marino
authors.forename: Carmen
authors.initials: C
authors.lastname: Festa
authors.forename: Maria
authors.initials: M
authors.lastname: Napolitano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castello
authors.forename: Armando
authors.initials: A
authors.lastname: Ialenti
authors.forename: Angela
authors.initials: A
authors.lastname: Ianaro
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007558:Italy; D027442:Laurus / Q000737:chemistry*; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D045792:Norisoprenoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D006027:Glycosides; D016328:NF-kappa B; D045792:Norisoprenoids; D051636:X-Linked Inhibitor of Apoptosis Protein; C557426:lauroside B; D011065:Poly(ADP-ribose) Polymerases; D051550:I-kappa B Kinase