Comparative anti-viral and anti-proliferative activity of PGA1 and PGJ2 against HTLV-I-infected MT-2 cells

Autor: Isabella Faraoni, Antonella Puglianiello, Giulia Lanzilli, C D'Onofrio, Carla Amici, Enzo Bonmassar, M. G. Santoro
Rok vydání: 1992
Předmět:
Zdroj: International Journal of Cancer. 51:481-488
ISSN: 1097-0215
0020-7136
DOI: 10.1002/ijc.2910510324
Popis: Prostaglandin (PG) A and J exert anti-viral and anti-proliferative effects in a number of experimental models. In particular, multiple treatments with PGAs prevent in vitro the clonal selection of HTLV-l-infected and potentially transformed cord-blood-derived mononuclear cells. Proliferation of HTLV-I-infected leukemic T cells is refractory in most cases to conventional anti-blastic therapy. We examined whether these cyclo-pentenone PGs might control cell proliferation and/or alter virus replication also in HTLV-l-transformed cells. We show that PGA1 and PGJ2 can exert powerful control of proliferation of the HTLV-l-immortalized, virus-producing MT-2 cell line, in a concentration-dependent fashion. Cells were preferentially arrested at the G1/S interface by treatment with PGA1 or PGJ2 without any detectable cellular toxicity. The anti-proliferative effect of PG treatment was independent of the growth phase of MT-2 cells, since both asynchronous and synchronous cells were sensitive to treatment. This effect was accompanied by an increase in the synthesis of a 70 kDa heat-shock protein (HSP70). However, synthesis of HSP70 was induced to a much greater extent by PGJ2 than by PGA1 at the same concentration. Neither PGA1 or PGJ2 inhibited the transcription of HTLV-I in MT-2 cells, but treatment with PGJ2, and not with PGA1, moderately inhibited the synthesis of viral proteins, i.e., p40 Tax and p19 core proteins. Moreover, infection of recipient K562 cells was significantly inhibited after pre-treatment of MT-2 cells with PGJ2 14 hr before or co-treatment at the onset of the co-culture with K562 cells. This effect was not obtained when MT-2 cells were repeatedly pre-treated with PGJ2 for I week before co-culturing. This suggests that reduced infection could be related to impairment of some step in virus-transmission phase.
Databáze: OpenAIRE
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