Suppression of proline-directed protein kinase F-A potentiates apoptotic induction and greatly enhances chemosensitivity in human acute lymphoblasticleukemia cells

Citation
Cp. Hsu et al., Suppression of proline-directed protein kinase F-A potentiates apoptotic induction and greatly enhances chemosensitivity in human acute lymphoblasticleukemia cells, CANCER, 92(7), 2001, pp. 1753-1758
Citations number
17
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER
ISSN journal
0008543X → ACNP
Volume
92
Issue
7
Year of publication
2001
Pages
1753 - 1758
Database
ISI
SICI code
0008-543X(20011001)92:7<1753:SOPPKF>2.0.ZU;2-3
Abstract
BACKGROUND. Previously, the authors reported that specific antisense suppre ssion of overexpressed proline-directed protein kinase (PDPK) F-A enhances the chemosensitivity of various clinical anticancer drugs up to > 100-fold in human prostate carcinoma cells, suggesting an association of PDPK F-A wi th drug resistance in human malignancies. METHODS. In this report, by using a similar approach, the authors demonstra te further that the suppression of PDPK FA enhances even more dramatically the chemosensitivity of clinically used anticancer drugs in various types o f human acute lymphoblastic leukemia (ALL) cells. RESULTS. Compared with parental and control transfected cells, transduced A LL cells (both Jurkat and CCRF-CEM cells) with low levels of PDPK F-A displ ayed an enhanced sensitivity to vincristine, vinblastine, paclitaxel, metho trexate, doxorubicin, and daunorubicin. Estimation of the 50% inhibitory co ncentration (IC50) index further revealed that the transduced cells display ed up to > 3000-fold drug sensitivity, and there was a correlation between suppressed levels of PDPK F-A and drug sensitivity. A mechanistic study fur ther revealed that the enhanced chemosensitivity in transduced ALL cells wa s due mainly to the potentiation of apoptotic induction. CONCLUSIONS. Taken together, the results demonstrate that the suppression o f overexpressed PDPK F-A greatly enhances the chemosensitivity of various c linical anticancer drugs in both types of human ALL cells, providing initia l evidence for an important role of this PDPK in controlling multidrug resi stance of ALL. (C) 2001 American Cancer Society.