K. Kameda et al., The role of intracellular Ca2+ in apoptosis induced by hyperthermia and its enhancement by verapamil in U937 cells, INT J RAD O, 49(5), 2001, pp. 1369-1379
Citations number
50
Categorie Soggetti
Radiology ,Nuclear Medicine & Imaging","Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
Purpose: The relationship between apoptosis induced by 42 degreesC and 44 d
egreesC hyperthermia alone or in combination with verapamil and changes in
intracellular Ca2+ concentration ([Ca2+](i)) was investigated in U937 cells
.
Methods: Apoptosis induced by hyperthermia was assessed according to DNA fr
agmentation, nuclear morphologic changes, and expression of phosphatidylser
ine on the outside plasma cell membrane. These changes were measured by flo
w cytometry. The [Ca2+](i) of individual cells after hyperthermia was monit
ored by a digital image-analyzing technique using Fura-2.
Results: Hyperthermia-induced apoptosis reached a plateau after 6 h and was
found to be both time and temperature-dependent. DNA fragmentation was max
imum at 44 degreesC after 30 min. Verapamil enhanced the apoptosis induced
by 42 degreesC and 44 degreesC hyperthermia in normal cells and by 44 degre
esC hyperthermia in thermotolerant cells. The number of cells containing hi
gher [Ca2+](i) (more than 200 nM) was significantly increased by hypertherm
ia and further elevated by the addition of verapamil in both normal and the
rmotolerant cells. Apoptosis induced by hyperthermia was markedly decreased
by an intracellular Ca2+ chelator, BAPTA-AM, in a dose-dependent manner,
Conclusion: These results indicate that [Ca2+](i) increase plays a crucial
role in apoptosis induced by hyperthermia and the combined treatment with v
erapamil in normal and thermotolerant U937 cells. Furthermore, hyperthermia
-combined drug therapy has potential significance in cancer therapy. (C) 20
01 Elsevier Science Inc.