A Novel Anticancer Ribonucleoside, 1-(3-C-Ethynyl-β-D-ribo-pentofuranosyl)Cytosine, Enhances Radiation-Induced Cell Death in Tumor Cells

Radiation-induced apoptosis of tumor cells is facilitated by inhibition of the interaction between Survivin and Smac/DIABLO

“…In fact, we have reported that a novel anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofutanosyl)cytosine (ECyd), enhances radiation-induced apoptosis in human gastric adenocarcinoma MKN45 (p53 wild type), MKN28 (p53 mutation) and murine rectum adenocarcinoma Colon26 (p53 status unknown) cells. The decrease in the radiation-induced expression of Survivin, Bcl-2, cyclin B1 and Wee1 was partly responsible for the enhancement of radiation-induced apoptosis by ECyd regardless of p53 status and cell type in vitro [7] and in vivo [8]. Furthermore, in MKN45 and MKN28 cells, purvalanol A, a cyclin-dependent kinase inhibitor, also enhances radiation-induced cell killing through an increase of apoptosis by downregulation of inhibitor of apoptosis family (IAP) family members (Survivin and XIAP), Bcl-2 family members (Bcl-X L and Bcl-2), cyclin B1 and Wee1 [9].…”

“…Subconfluent cultures of the tumor cell lines were incubated with pAd vectors at MOI 50 and the virus was allowed to adhere for 1 h at 37°C. Then medium was added and the incubation was continued under the same conditions for an additional 7 24 h. For immunocytochemistry, the cells were fixed with 4% paraformaldehyde and analyzed for Survivin expression.…”

Inhibition of HIF-1α by the anticancer drug TAS106 enhances X-ray-induced apoptosis in vitro and in vivo

“…The high activity of UCK in tumour cells relative to normal cells (Maehara et al, 1982;Koizumi et al, 2001;Matsuda and Sasaki, 2004) gives TAS106 an advantage in specificity for tumour therapy. In earlier studies, we have shown that both apoptosis and loss of clonogenic survival are induced through the abrogation of arrest at the G 2 /M phase in X-irradiated human (MKN45 and MKN28) and murine (Colon26) tumour cells, as well as Chinese hamster V79 normal cells, when X-irradiation is combined with TAS106 treatment in vitro (Inanami et al, 2004;Iizuka et al, 2005). The radiosensitising effects of TAS106 were also seen in colon26-transplanted tumours and MKN45 xenografts in vivo (Yasui et al, 2007).…”

“…The detection of apoptotic cells was performed as described previously (Inanami et al, 2004). In brief, cells incubated for the indicated times after X-irradiation were collected by centrifugation.…”

“…It has been shown that HIF-1a exerts its antiapoptotic function by transcriptional activation of antiapoptotic proteins, that is, the Bcl-2 family and inhibitors of apoptosis (IAPs), such as survivin (Dong et al, 2003;Peng et al, 2006). In our recent studies, the inhibition of survivin expression by TAS106 was thought to mainly contribute to the radiosensitisation of apoptosis and the suppression of tumour growth in vitro and in vivo (Inanami et al, 2004;Yasui et al, 2007). Thus, it is possible to hypothesise that TAS106 controls HIF-1a expression and results in the suppression of antiapoptotic proteins, that is, its downstream transactivating factors.…”