title: Sensitivity of different resistant tumour cell lines to the two novel compounds (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate and (1E,3E)-1,4-bis(2-naphthyl)-2,3-dinitro-1,3-butadiene.
abstract: The inhibition of cell proliferation by methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (1-Naph-NMCB) and (1E,3E)-1,4-bis(2-naphthyl)-2,3-dinitro-1,3-butadiene (2-Naph-DNB) has been studied in vitro against four cell lines selected for their resistance to doxorubicin, cisplatin, taxol and 5-fluorouracil. In previous experiments both compounds showed good in vitro antiproliferative, cytotoxic and pro-apoptotic activities against cell lines of different histologic origin. The results of the experiments presented here suggest that 1-Naph-NMCB is able to overcome all of the different mechanisms of resistance showed by the resistant cell lines used for our experiments. On the contrary, when we used the taxol-resistant A549-T12 cell line, characterized by a mechanism of resistance due to a mutation of the target site of taxol on microtubules, it displayed a partial but significant cross-resistance to 2-Naph-DNB. Although the actual mechanism of this cross-resistance has not yet been definitively elucidated, our results from immunostaining of microtubules suggest that it may be linked to the presence of a shared target site for taxol and 2-Naph-DNB on microtubules.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, S.C. Terapia Immunologica, L.go R. Benzi 10, 16132 Genova, Italy. maurizio.viale@istge.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viale
authors.forename: Giovanni
authors.initials: G
authors.lastname: Petrillo
authors.forename: Massimo
authors.initials: M
authors.lastname: Maccagno
authors.forename: Patrizio
authors.initials: P
authors.lastname: Castagnola
authors.forename: Cinzia
authors.initials: C
authors.lastname: Aiello
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cordazzo
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mariggiò
authors.forename: Sushilkumar A
authors.initials: SA
authors.lastname: Jadhav
authors.forename: Lara
authors.initials: L
authors.lastname: Bianchi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leto
authors.forename: Egon
authors.initials: E
authors.lastname: Rizzato
authors.forename: Alessandro
authors.initials: A
authors.lastname: Poggi
authors.forename: Domenico
authors.initials: D
authors.lastname: Spinelli
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002070:Butadienes / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: C526370:1,4-bis(2-naphthyl)-2,3-dinitro-1,3-butadiene; D000970:Antineoplastic Agents; D002070:Butadienes; D005231:Fatty Acids, Unsaturated; D009281:Naphthalenes; D013778:Tetrazolium Salts; D013844:Thiazoles; C526679:methyl 2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate; C022616:thiazolyl blue