PMID: 11911485Mar 26, 2002Paper

Betulinic acid sensitization of low pH adapted human melanoma cells to hyperthermia

International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
P R WachsbergerD B Leeper

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 ...Continue Reading

Citations

Jun 10, 2014·Expert Opinion on Therapeutic Patents·René Csuk
Jan 24, 2012·Bioorganic & Medicinal Chemistry Letters·Challa SureshHimangshu S Bose
Jun 4, 2010·The Journal of Investigative Dermatology·Jarmo K LaihiaLasse Leino
Oct 18, 2008·Fitoterapia·Barthelemy NyasseBernd Schneider
Jun 3, 2015·Medicinal Research Reviews·Dong-Mei ZhangWen-Cai Ye
Mar 6, 2007·Critical Reviews in Oncology/hematology·David J Stewart
Nov 5, 2011·Journal of Medicinal Chemistry·Wang-Yong YangIgor V Alabugin
Jun 3, 2006·Natural Product Reports·Petr DzubakJan Sarek
Jan 16, 2010·Anti-cancer Drugs·Franziska B MullauerJan Paul Medema

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