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Effects of Structurally Related Flavonoids on hsp Gene Expression in Human Promyeloid Leukaemia Cells

Gordana Rusak3*, Herwig O. Gutzeit1 and Jutta Ludwig-Müller2


1
Institute of Zoology, TU Dresden, D-01062 Dresden, Germany

2Institute of Botany, TU Dresden, D-01062 Dresden, Germany
3Department of Biology, Faculty of Science, Marulićev trg 20/II, 10000 Zagreb, Croatia

Article history:

Received July 2, 2002
Accepted November 7, 2002

Key words:

hsp genes, flavonoids, leukaemia, HL-60, dietary supplements

Summary:

Quercetin is a known specific inhibitor of hsp70 synthesis and thus might be a potent agent for enhancing the selective cytotoxicity of heat on tumour cells. A comparative analysis of the effects of quercetin and five structurally related flavonoids on hsp90α, hsp70A, hsp60 and hsp27 gene expression was carried out using human myeloid leukaemia cells (HL-60). The cells were preincubated with 50 μM quercetin, kaempferol, myricetin, taxifolin, isorhamnetin, methylquercetagetin or 0.1 % DMSO (controls) for 24 h at 37 °C before heat shock treatment (43 °C for 30 min). Total RNA was isolated from heat-stressed and unstressed cells and analysed by RT-PCR. Hsp27 gene expression was inhibited by flavonoids more strongly than other hsp genes investigated in heat stressed as well as in unstressed cells. Among the hsp genes tested, only hsp60 was expressed above control level under the influence of taxifolin. Members of the hsp70 and hsp27 families are highly expressed in breast and lung cancer and leukaemias and they play a role in the acquired resistance to chemotherapy or radiation therapy combined with hyperthermia. Therefore, hsps present potential targets for cancer diagnosis and treatment. The present structure/ activity study indicates 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 provide a basis for further design of specific inhibitors of hsp gene expression.



*Corresponding author:    gordana@croatica.botanic.hr
                                                     ++385 1 48 43 851

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