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.
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.
Viale
Maurizio
M
Istituto Nazionale per la Ricerca sul Cancro, S.C. Terapia Immunologica, L.go R. Benzi 10, 16132 Genova, Italy. maurizio.viale@istge.it
Petrillo
Giovanni
G
Maccagno
Massimo
M
Castagnola
Patrizio
P
Aiello
Cinzia
C
Cordazzo
Cinzia
C
Mariggiò
Maria A
MA
Jadhav
Sushilkumar A
SA
Bianchi
Lara
L
Leto
Giuseppe
G
Rizzato
Egon
E
Poggi
Alessandro
A
Spinelli
Domenico
D
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
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