Targeting the hypoxia pathway in malignant plasma cells by using 17-allylamino-17-demethoxygeldanamycin

• Authors: Kinga Kocemba-Pilarczyk , Barbara Ostrowska , Sonia Trojan , Ecce Aslan , Dorota Kusior , Małgorzata Lasota , Claire Lenouvel , Joanna Dulińska-Litewka
• Languages of publication: EN

Abstracts

EN

Multiple myeloma (MM) is characterized as a clonal expansion of malignant plasma cells in the bone marrow, which is often associated with pancytopenia and osteolytic bone disease. Interestingly, myeloma-infiltrated bone marrow is considered to be hypoxic, providing selection pressure for a developing tumour. Since HSP90 was shown to participate in stabilization of the subunit of the key transcription factor HIF-1, which controls the hypoxic response, the aim of this study was to investigate the influence of a HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), on MM cells cultured under low oxygenation conditions. We confirmed that 17-AAG inhibits hypoxic induction of the HIF-1 target genes in malignant plasma cells and demonstrate the concentration range of severe hypoxia-specific cytotoxicity. Next, we selected the malignant plasma cells under severe hypoxia/re-oxygenation culture conditions in the presence or absence of 17-AAG and subsequently, the cells which survived were further expanded and analyzed. Interestingly, we have noticed significant changes in the survival and the response to anti-MM drugs between the parental cell lines and those selected in cyclic severe hypoxia in the presence and absence of 17-AAG. Importantly, we also observed that the lack of oxygen itself, irrespectively of HIF-1 inhibition, is the main/pivotal factor driving the selection process in the experiments presented here.

Keywords

EN

Multiple myeloma; HIF-1; hypoxia; 17-AAG

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2018
• Volume: 65
• Issue: 1
• Pages: 101-109

Dates

published

2018

received

2017-08-11

revised

2017-11-28

accepted

2017-12-13

(unknown)

2018-03-15

Contributors

author

Kinga Kocemba-Pilarczyk

• Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland

author

Barbara Ostrowska

• Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland

author

Sonia Trojan

• Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland

author

Ecce Aslan

• Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland

author

Dorota Kusior

• Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland

author

Małgorzata Lasota

• Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland

author

Claire Lenouvel

• Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland

author

Joanna Dulińska-Litewka

• Chair of Medical Biochemistry, Jagiellonian University Medical College, Kraków, Poland

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Identifiers

DOI

10.18388/abp.2017_1630