Abstract
The potential of the calcium-entry blocker flunarizine in modulating the cytotoxicity of doxorubicin was investigated in human colon-adenocarcinoma cell lines sensitive to (LoVo) or with experimentally induced resistance (LoVo/DX) to doxorubicin. Exposure to 1 to 2 μg/ml flunarizine for intervals of up to 24 hr did not affect cell survival in either line. Simultaneous exposure to flunarizine and doxorubicin for 1 hr selectively enhanced doxorubicin activity in the resistant cell line and not in the sensitive cell line. In particular, the doxorubicin concentration able to reduce cell survival by 50% dropped to one third. Moreover, simultaneous exposure to flunarizine significantly increased intracellular doxorubicin accumulation, as evaluated by fluorescence spectrophotometry. Again, flow-cytometric analysis showed hyperpolarization of the membrane in resistant cells, starting from 15 min of exposure to 2 μg/ml flunarizine. Finally, in LoVo/DX cells, which normally express gp170, a 24-hr treatment with flunarizine markedly reduced the immunoreactivity of cells with 2 monoclonal antibodies (MAb57 and MRK16) directed against different external epitopes of the glycoprotein. The results from our study indicate the ability of flunarizine to positively modulate doxorubicin-resistance in human colon-adenocarcinoma cells expressing the multidrug-resistance phenotype.
| Original language | English |
|---|---|
| Pages (from-to) | 636-639 |
| Number of pages | 4 |
| Journal | International Journal of Cancer |
| Volume | 55 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1993 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Flunarizine as a modulator of doxorubicin resistance in human colon-adenocarcinoma cells. / Silvestrini, R.; Zaffaroni, N.; Costa, A.; Orlandi, L.; Villa, R.; Hendriks, H. R.
In: International Journal of Cancer, Vol. 55, No. 4, 1993, p. 636-639.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Flunarizine as a modulator of doxorubicin resistance in human colon-adenocarcinoma cells
AU - Silvestrini, R.
AU - Zaffaroni, N.
AU - Costa, A.
AU - Orlandi, L.
AU - Villa, R.
AU - Hendriks, H. R.
PY - 1993
Y1 - 1993
N2 - The potential of the calcium-entry blocker flunarizine in modulating the cytotoxicity of doxorubicin was investigated in human colon-adenocarcinoma cell lines sensitive to (LoVo) or with experimentally induced resistance (LoVo/DX) to doxorubicin. Exposure to 1 to 2 μg/ml flunarizine for intervals of up to 24 hr did not affect cell survival in either line. Simultaneous exposure to flunarizine and doxorubicin for 1 hr selectively enhanced doxorubicin activity in the resistant cell line and not in the sensitive cell line. In particular, the doxorubicin concentration able to reduce cell survival by 50% dropped to one third. Moreover, simultaneous exposure to flunarizine significantly increased intracellular doxorubicin accumulation, as evaluated by fluorescence spectrophotometry. Again, flow-cytometric analysis showed hyperpolarization of the membrane in resistant cells, starting from 15 min of exposure to 2 μg/ml flunarizine. Finally, in LoVo/DX cells, which normally express gp170, a 24-hr treatment with flunarizine markedly reduced the immunoreactivity of cells with 2 monoclonal antibodies (MAb57 and MRK16) directed against different external epitopes of the glycoprotein. The results from our study indicate the ability of flunarizine to positively modulate doxorubicin-resistance in human colon-adenocarcinoma cells expressing the multidrug-resistance phenotype.
AB - The potential of the calcium-entry blocker flunarizine in modulating the cytotoxicity of doxorubicin was investigated in human colon-adenocarcinoma cell lines sensitive to (LoVo) or with experimentally induced resistance (LoVo/DX) to doxorubicin. Exposure to 1 to 2 μg/ml flunarizine for intervals of up to 24 hr did not affect cell survival in either line. Simultaneous exposure to flunarizine and doxorubicin for 1 hr selectively enhanced doxorubicin activity in the resistant cell line and not in the sensitive cell line. In particular, the doxorubicin concentration able to reduce cell survival by 50% dropped to one third. Moreover, simultaneous exposure to flunarizine significantly increased intracellular doxorubicin accumulation, as evaluated by fluorescence spectrophotometry. Again, flow-cytometric analysis showed hyperpolarization of the membrane in resistant cells, starting from 15 min of exposure to 2 μg/ml flunarizine. Finally, in LoVo/DX cells, which normally express gp170, a 24-hr treatment with flunarizine markedly reduced the immunoreactivity of cells with 2 monoclonal antibodies (MAb57 and MRK16) directed against different external epitopes of the glycoprotein. The results from our study indicate the ability of flunarizine to positively modulate doxorubicin-resistance in human colon-adenocarcinoma cells expressing the multidrug-resistance phenotype.
UR - http://www.scopus.com/inward/record.url?scp=0027372048&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027372048&partnerID=8YFLogxK
U2 - 10.1002/ijc.2910550420
DO - 10.1002/ijc.2910550420
M3 - Article
C2 - 8406992
AN - SCOPUS:0027372048
VL - 55
SP - 636
EP - 639
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 4
ER -