ABSTRACT
Voltage-gated K+ (Kv) channels have been considered to be a regulator of membrane potential and neuronal excitability. Recently, accumulated evidence has indicated that several Kv channel subtypes contribute to the control of cell proliferation in various types of cells and are worth noting as potential emerging molecular targets of cancer therapy. In the present study, we investigated the effects of the Kv1.1-specific blocker, dendrotoxin-kappa (DTX-kappa), on tumor formation induced by the human lung adenocarcinoma cell line A549 in a xenograft model. Kv1.1 mRNA and protein was expressed in A549 cells and the blockade of Kv1.1 by DTX-kappa, reduced tumor formation in nude mice. Furthermore, treatment with DTX-kappa significantly increased protein expression of p21Waf1/Cip1, p27Kip1, and p15INK4B and significantly decreased protein expression of cyclin D3 in tumor tissues compared to the control. These results suggest that DTX-kappa has anti-tumor effects in A549 cells through the pathway governing G1-S transition.
Subject(s)
Animals , Humans , Mice , Adenocarcinoma/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Disease Models, Animal , Elapid Venoms/pharmacology , Elapidae , /antagonists & inhibitors , Lung Neoplasms/drug therapy , Mice, Nude , Neoplasm Transplantation , Potassium Channel Blockers/pharmacology , RNA, Messenger/genetics , Transplantation, HeterologousABSTRACT
The vibrational spectral differences of normal and lung cancer cells were studied for the development of effective cancer cell screening by means of attenuated total reflection infrared spectroscopy. The phosphate monoester symmetric stretching nus(PO3(2-)) band intensity at ~970 cm-1 and the phosphodiester symmetric stretching nus(PO2-) band intensity at ~1,085 cm-1 in nucleic acids and phospholipids appeared to be significantly strengthened in lung cancer cells with respect to the other vibrational bands compared to normal cells. This finding suggests that more extensive phosphorylation occur in cancer cells. These results demonstrate that lung cancer cells may be prescreened using infrared spectroscopy tools.