Abstract
The effect of thaliblastine (TBL, NSC-68075), a plant alkaloid, in overcoming multidrug resistance was investigated in doxorubicin (ADR)-resistant murine leukemic P388/R-84 cells. In the soft agar clonogenic assay, a nontoxic concentration of TBL (2 μM) reduced the 50% inhibitory dose of ADR (1-h exposure) from 10.8 to 1.4 μM with a dose modification factor of 7.7. Continuous treatment of P388/R-84 cells with ADR and TBL for 24 h further lowered the 50% inhibitory dose from 3.5 to 0.07 μM, the resistance level being decreased from 233-fold in the absence of TBL to 4.7-fold in the presence of TBL as compared to the parental P388 cells. Although ADR or TBL individually had no detectable effects on cell cycle traverse, the combination of the two drugs caused a significant G2 block. Flow cytometric analysis showed that TBL enhanced ADR retention in P388/R-84 cells in a dose- and time-dependent manner. TBL partially blocked the photolabeling of P-glycoprotein with [3H]azidopine, and this blocking effect was further enhanced in combination with ADR. Our results indicate that TBL can reverse multidrug resistance by direct interaction with P-glycoprotein, thereby increasing cellular ADR retention.
| Original language | English |
|---|---|
| Pages (from-to) | 2544-2547 |
| Number of pages | 4 |
| Journal | Cancer Research |
| Volume | 53 |
| Issue number | 11 |
| State | Published - Jun 1 1993 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Thaliblastine, a plant alkaloid, circumvents multidrug resistance by direct binding to P-glycoprotein. / Chen, Guan; Ramachandran, Cheppail; Krishan, Awtar.
In: Cancer Research, Vol. 53, No. 11, 01.06.1993, p. 2544-2547.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Thaliblastine, a plant alkaloid, circumvents multidrug resistance by direct binding to P-glycoprotein
AU - Chen, Guan
AU - Ramachandran, Cheppail
AU - Krishan, Awtar
PY - 1993/6/1
Y1 - 1993/6/1
N2 - The effect of thaliblastine (TBL, NSC-68075), a plant alkaloid, in overcoming multidrug resistance was investigated in doxorubicin (ADR)-resistant murine leukemic P388/R-84 cells. In the soft agar clonogenic assay, a nontoxic concentration of TBL (2 μM) reduced the 50% inhibitory dose of ADR (1-h exposure) from 10.8 to 1.4 μM with a dose modification factor of 7.7. Continuous treatment of P388/R-84 cells with ADR and TBL for 24 h further lowered the 50% inhibitory dose from 3.5 to 0.07 μM, the resistance level being decreased from 233-fold in the absence of TBL to 4.7-fold in the presence of TBL as compared to the parental P388 cells. Although ADR or TBL individually had no detectable effects on cell cycle traverse, the combination of the two drugs caused a significant G2 block. Flow cytometric analysis showed that TBL enhanced ADR retention in P388/R-84 cells in a dose- and time-dependent manner. TBL partially blocked the photolabeling of P-glycoprotein with [3H]azidopine, and this blocking effect was further enhanced in combination with ADR. Our results indicate that TBL can reverse multidrug resistance by direct interaction with P-glycoprotein, thereby increasing cellular ADR retention.
AB - The effect of thaliblastine (TBL, NSC-68075), a plant alkaloid, in overcoming multidrug resistance was investigated in doxorubicin (ADR)-resistant murine leukemic P388/R-84 cells. In the soft agar clonogenic assay, a nontoxic concentration of TBL (2 μM) reduced the 50% inhibitory dose of ADR (1-h exposure) from 10.8 to 1.4 μM with a dose modification factor of 7.7. Continuous treatment of P388/R-84 cells with ADR and TBL for 24 h further lowered the 50% inhibitory dose from 3.5 to 0.07 μM, the resistance level being decreased from 233-fold in the absence of TBL to 4.7-fold in the presence of TBL as compared to the parental P388 cells. Although ADR or TBL individually had no detectable effects on cell cycle traverse, the combination of the two drugs caused a significant G2 block. Flow cytometric analysis showed that TBL enhanced ADR retention in P388/R-84 cells in a dose- and time-dependent manner. TBL partially blocked the photolabeling of P-glycoprotein with [3H]azidopine, and this blocking effect was further enhanced in combination with ADR. Our results indicate that TBL can reverse multidrug resistance by direct interaction with P-glycoprotein, thereby increasing cellular ADR retention.
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M3 - Article
VL - 53
SP - 2544
EP - 2547
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 11
ER -