Betulinic acid sensitization of low pH adapted human melanoma cells to hyperthermia
| Autor: | Dennis B. Leeper, Miriam L. Wahl, Randy Burd, Phyllis R. Wachsberger |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Hyperthermia
Cancer Research Cell Survival Physiology Apoptosis Biology chemistry.chemical_compound Physiology (medical) Betulinic acid Tumor Cells Cultured medicine Humans Viability assay Betulinic Acid Cytotoxicity Melanoma Hyperthermia Induced Hydrogen-Ion Concentration medicine.disease Molecular biology Triterpenes Enzyme Activation Terminal deoxynucleotidyl transferase chemistry Biochemistry Cell culture Caspases DNA fragmentation Poly(ADP-ribose) Polymerases Pentacyclic Triterpenes |
| Zdroj: | International Journal of Hyperthermia. 18:153-164 |
| ISSN: | 1464-5157 0265-6736 |
| DOI: | 10.1080/02656730110091333 |
| Popis: | Betulinic acid is a known inducer of apoptosis in human melanoma that is most effective under conditions of low pH. It was hypothesized that betulinic acid, in combination with acute acidification and/or hyperthermia, would induce higher levels of apoptosis and cytotoxicity in low pH-adapted human melanoma cells than in cells grown at pH 7.3. DB-1 human melanoma cells, adapted to a tumour-like growth pH of 6.7, were exposed to hyperthermia (2h at 42 degrees C) and/or betulinic acid (4-10 microg/ml) and compared with cells grown at a physiological pH of 7.3 or after acute acidification from pH 7.3-6.3 or pH 6.7-6.3. Betulinic acid induced higher levels of apoptosis and cytotoxicity in low pH-adapted cells than in cells grown at pH 7.3, as measured by the terminal deoxynucleotidyl transferase (TdT) DNA fragmentation assay (TUNEL), the MTS cell viability assay, and single cell survival. Acute acidification of low pH adapted cells rendered them more susceptible to betulinic acid-induced apoptosis and cytotoxicity. In the presence of hyperthermia at 42 degrees C for 2 h, cells grown at pH 7.3 were not sensitized to heat killing by betulinic acid, whereas cells grown at pH 7.3 and acutely acidified to pH 6.3, cells adapted to growth at pH 6.7 and cells adapted to growth at pH 6.7 and acutely acidified to pH 6.3 were all similarly sensitized to heat killing by betulinic acid, with survival values of 5, 9 and 2%, respectively. It is concluded that betulinic acid may be useful in potentiating the therapeutic efficacy of hyperthermia as a cytotoxic agent in acidotic areas of tumours with minimal effect in normal tissues growing at pH 7.3. |
| Databáze: | OpenAIRE |
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