Naslov
Effects of structurally related flavonoids on hsp gene expression in human promyeloid leukaemia cells

Autori
Rusak, Gordana ; Gutzeit, Herwig O ; Ludwig Müller, Jutta

Izvornik
Food Technology and Biotechnology (1330-9862) 40 (2002), 4; 267-273

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
hsp genes; flavonoids; leukaemia; HL-60; dietary supplements

Sažetak
Quercetin is a known specific inhibitor of hsp70 synthesis and thus might be a potent agent for enhancing the selective cytotoxicity of heat on tumor cells. A comparative analysis of the effects of quercetin and five structurally related flavonoids on hsp90&#61537 ; ; ; , hsp70A, hsp60 and hsp27 gene expression was carried out using human myeloid leukaemia cells (HL-60). The cells were preincubated with 50&micro ; ; ; M quercetin, kaempferol, myricetin, taxifolin, isorhamnetin, methylquercetagetin or 0, 1% DMSO (controls) for 24 h at 37 &#61616 ; ; ; C before heat shock treatment (43 &ordm ; ; ; C for 30 min). Total RNA was isolated from heat-stressed and not heat-stressed cells and analysed by RT-PCR. Hsp27 gene expression was stronger inhibited by flavonoids than other hsp genes investigated in heat stressed as well as in not stressed cells. Among the hsp genes tested only hsp60 was expressed over control level by influence of taxifolin. Members of the hsp70 and hsp27 families are highly expressed in breast and lung cancer and leukaemias. High level of hsp70 and hsp27 expression in patients with cancer is associated with resistance to chemotherapy or radiation therapy combined with hypertermia. Elevated hsp27 protein level may increase invasiveness of human breast cancer cells. Therefore, hsps present potential targets for cancer diagnosis and treatmant. Present structure/activity study indicated that position, number and substitution of hydroxyl groups of the B ring and saturation of the C2-C3 bond are important factors affecting flavonoid activity on hsp gene expression. This study could help to provide a basis for the futher design of specific inhibitors of hsp gene expression.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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