Quercetin sensitizes cells in a tumour-like low pH environment to hyperthermia

Phyllis R. Wachsberger, Randy M Burd, A. Bhala, S. B. Bobyock, M. L. Wahl, C. S. Owen, S. B. Rifat, D. B. Leeper

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Quercetin has been shown to act as a hyperthermia sensitizer by inhibiting the synthesis of heat shock protein 70 (HSP70) in a variety of tumour cell lines. It is most effective under conditions of low pH. This study was designed to test the hypothesis that quercetin suppresses thermotolerance development in cells adapted to growth at low pH and renders them as responsive as acutely acidified cells to hyperthermia-induced cytotoxicity. Chinese hamster ovarian carcinoma cells (OvCa) were exposed to 42°C hyperthermia and/or quercetin (50-200 μm) at their growth pH of either 7.3 or 6.7 or after acute acidification from 7.3 to 6.7. Thermotolerance development was measured by colony survival. HSP70 synthesis and total protein synthesis were measured by radioactive precursor pulse labelling techniques. Quercetin, in a concentration-dependent manner, reduced the rate of total protein synthesis and increased cytotoxicity equally after acute acidification to pH 6.7 or growth at pH 6.7 at 37°C, and to a greater extent than it did in cells at pH 7.3. At 42°C, 100 μm quercetin inhibited total protein synthesis, HSP70 synthesis and thermotolerance development to a similar extent in cells grown at pH 6.7 or acutely acidified to pH 6.7. In contrast, quercetin reduced but did not completely inhibit HSP70 synthesis and thermotolerance development in cells grown and heated at pH 7.3. These results support the hypothesis that quercetin can specifically reduce thermotolerance development in tumour cells adapted to growth at pHe 6.7 so that they respond similarly to acutely acidified cells. Since many tumours are adapted to growth at low pH and may resist a wide variety of therapeutic modalities, inhibition of thermotolerance expression by quercetin may not only enhance the response to hyperthermia but the response to commonly used therapies such as chemotherapy and radiation.

Original languageEnglish (US)
Pages (from-to)507-519
Number of pages13
JournalInternational Journal of Hyperthermia
Volume19
Issue number5
DOIs
StatePublished - Sep 2003
Externally publishedYes

Fingerprint

Quercetin
Fever
HSP70 Heat-Shock Proteins
Neoplasms
Growth
Induced Hyperthermia
Proteins
Cricetulus
Tumor Cell Line
Thermotolerance
Radiation
Carcinoma
Drug Therapy

Keywords

  • HSP70
  • Hyperthermia
  • pH
  • Quercetin
  • Thermotolerance

ASJC Scopus subject areas

  • Cancer Research
  • Radiological and Ultrasound Technology

Cite this

Wachsberger, P. R., Burd, R. M., Bhala, A., Bobyock, S. B., Wahl, M. L., Owen, C. S., ... Leeper, D. B. (2003). Quercetin sensitizes cells in a tumour-like low pH environment to hyperthermia. International Journal of Hyperthermia, 19(5), 507-519. https://doi.org/10.1080/0265673031000078697

Quercetin sensitizes cells in a tumour-like low pH environment to hyperthermia. / Wachsberger, Phyllis R.; Burd, Randy M; Bhala, A.; Bobyock, S. B.; Wahl, M. L.; Owen, C. S.; Rifat, S. B.; Leeper, D. B.

In: International Journal of Hyperthermia, Vol. 19, No. 5, 09.2003, p. 507-519.

Research output: Contribution to journalArticle

Wachsberger, PR, Burd, RM, Bhala, A, Bobyock, SB, Wahl, ML, Owen, CS, Rifat, SB & Leeper, DB 2003, 'Quercetin sensitizes cells in a tumour-like low pH environment to hyperthermia', International Journal of Hyperthermia, vol. 19, no. 5, pp. 507-519. https://doi.org/10.1080/0265673031000078697
Wachsberger, Phyllis R. ; Burd, Randy M ; Bhala, A. ; Bobyock, S. B. ; Wahl, M. L. ; Owen, C. S. ; Rifat, S. B. ; Leeper, D. B. / Quercetin sensitizes cells in a tumour-like low pH environment to hyperthermia. In: International Journal of Hyperthermia. 2003 ; Vol. 19, No. 5. pp. 507-519.
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