Anti-proliferative effect of interferon-gamma is enhanced by iron chelation in colon cancer cell lines in vitro.
OBJECTIVE
The receptor of interferon-gamma (IFN-gammaR) consists of IFN-gammaR1 and R2. Resistance to the anti-proliferative effect of IFN-gamma is due to downregulation of IFN-gammaR2. The aim of this study was to investigate whether iron chelation could upregulate IFN-gammaR2 and enhance the anti-proliferative effect of IFN-gamma in colon cancer cell lines.


METHODS
The colon cancer cell lines, SW480, COLO, and WiDr were treated with the iron chelating agent DFO, and the expression of IFN-gammaR1 and IFN-gammaR2 was evaluated by FACS. The anti-proliferative effect of IFN-gamma was investigated by MTT assay, and the proapoptotic effect was investigated by FACS with Annexin-V.


RESULTS
FACS demonstrated that DFO increased the expression of IFN-gammaR2, whereas the effect on IFN-gammaR1 expression was less marked. MTT assay showed that cell growth was inhibited by DFO. Addition of DFO and IFN-gamma inhibited further, but inhibition was not observed with IFN-gamma alone. Apoptotic cells were increased by DFO, and further increased with DFO + IFN-gamma together.


CONCLUSIONS
Expression of IFN-gammaR2 is restored by iron chelation, and the increased expression of IFN-gammaR2 enhances the anti-proliferative effect of IFN-gamma through induction of apoptosis in colon cancer cells.
Mori
Shozo
S
Second Department of Surgery, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan.
Sawada
Tokihiko
T
Okada
Toshie
T
Kubota
Keiichi
K
D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003676:Deferoxamine / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D017471:Receptors, Interferon / Q000187:drug effects* / Q000378:metabolism*; D017262:Siderophores / Q000494:pharmacology*; D000096743:Interferon gamma Receptor
D000970:Antineoplastic Agents; D003676:Deferoxamine; D007371:Interferon-gamma; D017471:Receptors, Interferon; D017262:Siderophores; D000096743:Interferon gamma Receptor