Naslov
Differential anti-proliferative mechanisms of novel derivative of benzimidazo[1,2-a]quinoline in colon cancer cells depending on their p53 status

Autori
Sedić, Mirela ; Poznić, Miroslav ; Gehrig, Peter ; Scott, Mike ; Schlapbach, Ralph ; Hranjec, Marijana ; Karminski-Zamola, Grace ; Pavelić, Krešimir ; Kraljević Pavelić, Sandra

Izvornik
Molecular cancer therapeutics (1535-7163) 7 (2008), 7; 2121-2132

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
quinoline ; proteomics ; colon cancer ; p53 ; chemotherapeutic

Sažetak
In the present paper, we describe a mechanistic study of a novel derivative of Namidino- substituted benzimidazo[1, 2-a] quinoline in two human colorectal cancer cell lines differing in p53 gene status. We used a proteomic approach based on twodimensional gel electrophoresis coupled with mass spectrometry to complement the results obtained by common molecular biology methods for analyzing cell proliferation, cell cycle and apoptosis. Tested quinoline derivative inhibited colon cancer cell growth, whereby p53 gene status seemed to be critical for its differential response patterns. DNA damage and oxidative stress are likely to be the common triggers of molecular events underlying its anti-proliferative effects. In HCT 116 (wild-type p53), this compound induced a p53-dependent response resulting in accumulation of the G1 and S phase cells and induction of apoptosis via both, caspase-3-dependent and caspase-independent pathways. Quinoline derivative triggered transient, p53-independent G2/M arrest in mutant p53 cells (SW620) and succeeding mitotic transition, whereby these cells underwent cell death, probably due to aberrant mitosis (mitotic catastrophe). Proteomic approach used in this study proved to be a valuable tool for investigating cancer cell response to newly synthesized compound, as it specifically unraveled some molecular changes that would not have been otherwise detected, e.g., up-regulation of the p53- dependent chemotherapeutic response marker maspin in HCT 116 and impairment in ribosome biogenesis in SW620. Finally, anti-proliferative effects of tested quinoline derivative on SW620 cells strongly support its possible role as an anti-metastatic agent and encourage further in vivo studies on the chemotherapeutic potential of this compound against colorectal carcinoma.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA