Novel dinuclear platinum(II) complexes targets NFkappaB signaling pathway to induce apoptosis and inhibit metabolism of MCF-7 breast cancer cells.
Four novel dinuclear platinum(II) complexes of formula [Pt2L4(berenil)2]Cl4 (Pt1-Pt4) where L is piperazine (Pt1), 4-picoline (Pt2), 3-picoline (Pt3) or isopropylamine (Pt4) were compared to cisplatin in respect to collagen biosynthesis, beta1- integrin receptor, IGF-I receptor, phosphorylated MAP-kinases (ERK1/ERK2 and p38), phosphorylated Akt kinase expression and appearance of apoptosis in MCF-7 breast cancer cells. It was found that Pt1-Pt4 were more active inhibitor of collagen biosynthesis than cisplatin. The expression of IGF-I and beta1 integrin receptor, as well as phosphorylated MAPK, (ERK1 and ERK2 and p38) was significantly increased in cells incubated for 24 h with 20 muM Pt1-Pt4 compared to the control, not treated cells. The phenomenon was related to the increase expresion of NFkappaB by Pt1-Pt4 as shown by Western immunoblot analysis. Experiments made with annexin V-FITC and detection of apoptosis by a fluorescent microscopy assay revealed that novel dinuclear platinum(II) complexes (Pt1-Pt4) inhibited the proliferation of MCF-7 breast cancer cells by increasing the number of apoptotic and necrotic cells.
Popławska
Bozena
B
Department of Biotechnology, Medical University of Białystok, Białystok, Poland.
Bielawska
Anna
A
Surazyński
Arkadiusz
A
Czarnomysy
Robert
R
Bielawski
Krzysztof
K
D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D010984:Platinum; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D016328:NF-kappa B; D009944:Organoplatinum Compounds; D010984:Platinum