Fendiline, an anti-anginal drug, increases intracellular Ca2+ in PC3 human prostate cancer cells.
BACKGROUND
The effects of the anti-anginal drug fendiline on intracellular Ca2+ concentrations ([Ca2+]i) in human PC3 prostate cancer cells were examined.


METHODS
[Ca2+]i was measured using the fluorescent dye fura-2.


RESULTS
Fendiline (0.5-100 microM) increased [Ca2+]i in a concentration-dependent manner. Ca2+ removal partly inhibited the Ca2+ signals. In Ca2+-free medium, pretreatment with 100 microM fendiline inhibited most of the [Ca2+]i increase induced by 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), and pretreatment with thapsigargin abolished the fendiline-induced [Ca2+]i increases. Adding 3 mM Ca2+ increased [Ca2+]i in cells pretreated with 0.5-200 microM fendiline in Ca2+-free medium. Pretreatment with 1 microM U73122 to block the formation of inositol-1.4.5-trisphosphate (IP3) did not alter fendiline-induced internal Ca2+ release.


CONCLUSIONS
The anti-anginal drug fendiline induced internal Ca2+ release and external Ca2+ entry. Because prolonged increases in [Ca2+]i may lead to cell injury and death, the long-term effect of fendiline on the function of prostate cancer cells should be investigated.
Jan
C R
CR
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Taiwan.
Lee
K C
KC
Chou
K J
KJ
Cheng
J S
JS
Wang
J L
JL
Lo
Y K
YK
Chang
H T
HT
Tang
K Y
KY
Yu
C C
CC
Huang
J K
JK
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005275:Fendiline / Q000494:pharmacology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D005275:Fendiline; D002118:Calcium