Novel dinuclear platinum(II) complexes targets NFkappaB signaling pathway to induce apoptosis and inhibit metabolism of MCF-7 breast cancer cells.

Abstract

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.

• Authors: Bozena Popławska, Anna Bielawska, Arkadiusz Surazyński, Robert Czarnomysy, Krzysztof Bielawski
• Journal: Folia histochemica et cytobiologica (Folia Histochem Cytobiol) Vol. 47 Issue 5 Pg. S141-6 ( 2009) ISSN: 1897-5631 [Electronic] Poland
• PMID: 20067886 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• NF-kappa B
• Organoplatinum Compounds
• Platinum

Topics

• Antineoplastic Agents (chemistry)
• Apoptosis (drug effects)
• Breast Neoplasms (metabolism)
• Cell Line, Tumor
• Humans
• MCF-7 Cells
• NF-kappa B (metabolism)
• Organoplatinum Compounds (therapeutic use)
• Platinum
• Signal Transduction (drug effects)