Back to Search
Start Over
Betulinic acid sensitization of low pH adapted human melanoma cells to hyperthermia
- Source :
- International Journal of Hyperthermia. 18:153-164
- Publication Year :
- 2002
- Publisher :
- Informa UK Limited, 2002.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14645157 and 02656736
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- International Journal of Hyperthermia
- Accession number :
- edsair.doi.dedup.....39c9ef9abfdc6ed340fddff3b51966bf