Naslov
Purine nucleoside phosphorylase gene expression in response to 9-deazaguanine and its derivative in human leukemia and lymphoma cells

Autori
Suver, Mirjana ; Žinić, Biserka ; Glavaš-Obrovac, Ljubica

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
33rd FEBS Congress & 11th IUBMB Conference Biochemistry of Cell Regulation : abstracts ; u: The FEBS Journal 275 (2008) (S1) ; Poster presentations 99-436 ; B. Nuclear Receptors and Control of Transcription, PP2B-31 / Perham, Richard - Oxford : Wiley-Blackwell, 2008, 142-142

Skup
FEBS Congress (33 ; 2008) : IUBMB Conference Biochemistry of Cell Regulation (11 ; 2008)

Mjesto i datum
Atena, Grčka, 28.06.2008. - 03.07.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
9-deazaguanine derivative; PNP; gene expression; cell cycle; enzyme activity

Sažetak
Recent studies of cytotoxic activity of 9-deazaguanine (9-DG) and its derivative, 1-methyl-9-deazaguanine (AG-19-K1) showed promise inhibitory effects against leukemia and lymphoma cells. Their potent intracellular target could be purine nucleoside phosphorylase (PNP), which is overexpressed in the most of T-cells diseases. Three leukemia and lymphoma cell lines (K562, JURKAT and HuT78) were treated by 9-DG and AG-19-K1 during 6, 12 and 24h. PNP enzymatic activity was analyzed in cell lysates using TLC with [8-14C]inosine as a substrate. Expression of pnp, caspase-3 and p53 gene was assayed by RT-PCR. After cell fixation and PI dye cell cycle was also analyzed. Exposure of cells to compounds caused statistically significant (p<0.05) decrease of pnp gene expression in all treated cells in a time-dependent manner. AG-19-K1 increased expression of caspase-3 in HuT78 cells while p53 was not expressed. On the contrary, in JURKAT cells, AG-19-K1 increased expression of p53 after 6 and 24h of treatment. Cell cycle analyses of K562 showed that both substances led to the cell arrest in G1/G0 phase after 12h of treatment. Although novel compounds were synthesized as potential PNP inhibitors, they had no influence on PNP catalytic activity. 9-dezagvanine and its derivative change expression of pnp gene and have influence on purine salvage pathway in human leukemia and lymphoma cells. For better understanding further investigation is needed.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti

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