TY - JOUR
T1 - Kt-5720 reverses multidrug resistance in variant S49 mouse lymphoma cells transduced with the human MDR1 cDNA and in human multidrug-resistant carcinoma cells
AU - Galski, H.
AU - Lazarovici, P.
AU - Gottesman, M. M.
AU - Murakata, C.
AU - Matsuda, Y.
AU - Hochman, J.
PY - 1995
Y1 - 1995
N2 - T-25-Adh cells, cell variants derived from S49 mouse lymphoma, were transduced with a retrovirus containing the human MDR1 cDNA. The resultant cells (HU-1) are cross-resistant to colchicine, doxorubicin, vinblastine and actinomycin D, and their resistance to colchicine is reversed by verapamil. HU-1 cells were used to screen several protein kinase modulators for their ability to reverse multidrug resistance. Among the tested indole carbazole (K-252a) family of protein kinase inhibitors, only the antibiotic alkaloid KT-5720 (9-n-hexyl derivative of K-252a) could overcome the multidrug resistance of HU-1 cells and KB-V1 human carcinoma cells. Since other protein kinase A, C and G modulators did not reverse multidrug resistance in the tested multidrug-resistant cells, the chemosensitising activity of KT-5720 on these cells is apparently independent of its kinase inhibitory effects. Since KT-5720 fully reversed multidrug resistance at non-toxic concentrations, it might be a candidate for clinical chemosensitisation in combination chemotherapy.
AB - T-25-Adh cells, cell variants derived from S49 mouse lymphoma, were transduced with a retrovirus containing the human MDR1 cDNA. The resultant cells (HU-1) are cross-resistant to colchicine, doxorubicin, vinblastine and actinomycin D, and their resistance to colchicine is reversed by verapamil. HU-1 cells were used to screen several protein kinase modulators for their ability to reverse multidrug resistance. Among the tested indole carbazole (K-252a) family of protein kinase inhibitors, only the antibiotic alkaloid KT-5720 (9-n-hexyl derivative of K-252a) could overcome the multidrug resistance of HU-1 cells and KB-V1 human carcinoma cells. Since other protein kinase A, C and G modulators did not reverse multidrug resistance in the tested multidrug-resistant cells, the chemosensitising activity of KT-5720 on these cells is apparently independent of its kinase inhibitory effects. Since KT-5720 fully reversed multidrug resistance at non-toxic concentrations, it might be a candidate for clinical chemosensitisation in combination chemotherapy.
KW - K-252a derivatives
KW - KT-5720
KW - MDR1
KW - P-glycoprotein
KW - chemosensitisers
KW - multidrug resistance
KW - protein kinase inhibitors
KW - protein kinases
UR - http://www.scopus.com/inward/record.url?scp=0028915160&partnerID=8YFLogxK
U2 - 10.1016/0959-8049(94)00511-3
DO - 10.1016/0959-8049(94)00511-3
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C2 - 7786606
AN - SCOPUS:0028915160
SN - 0959-8049
VL - 31
SP - 380
EP - 388
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 3
ER -
