The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis
Open accessAbstract
Multidrug resistance mediated by the drug efflux protein, P-glycoprotein (P-gp), is one mechanism that tumor cells use to escape death induced by chemotherapeutic agents. However, the mechanism by which P-gp confers resistance to a large variety of structurally diverse molecules has remained elusive. In this study, classical multidrug resistant human CEM and K562 tumor cell lines expressing high levels of P-gp were less sensitive to multiple forms of caspase-dependent cell death, including that mediated by cytotoxic drugs and ligation of Fas. The DNA fragmentation and membrane damage inflicted by these stimuli were defined as caspase dependent by various soluble peptide fluoromethylketone caspase inhibitors. Inhibition of P-gp function by the anti-P-gp mAb MRK-16 or verapamil could reverse resistance to these forms of cell death. Inhibition of P-gp function also enhanced drug or Fas-mediated activation of caspase-3 in drug-resistant CEM cells. By contrast, caspase-independent cell death events in the same cells, including those mediated by pore-forming proteins or intact NK cells, were not affected by P-gp expression. These observations suggest that, in addition to effluxing drugs, P-gp may play a specific role in regulating some caspase-dependent apoptotic pathways.
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Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., & Wang, X. (1997) · Cell · doi:10.1016/s0092-8674(00)80434-1 · Cited by 7,289
Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome c
Liu, X., Kim, C. N., Yang, J., Jemmerson, R., & Wang, X. (1996) · Cell · doi:10.1016/s0092-8674(00)80085-9 · Cited by 5,167
ABC Transporters: From Microorganisms to Man
Higgins, C. F. (1992) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.08.110192.000435 · Cited by 3,985
Nagata, S., & Golstein, P. (1995) · Science · doi:10.1126/science.7533326 · Cited by 3,979
BIOCHEMISTRY OF MULTIDRUG RESISTANCE MEDIATED BY THE MULTIDRUG TRANSPORTER
Gottesman, M. M., & Pastan, I. (1993) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.62.070193.002125 · Cited by 3,568
A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants
Juliano, R. L., & Ling, V. (1976) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/0005-2736(76)90160-7 · Cited by 3,296
Muzio, M., Chinnaiyan, A. M., Kischkel, F. C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, C., Bretz, J. D., Zhang, M., Gentz, R., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81266-0 · Cited by 3,046
Schinkel, A. H., Smit, J. J. M., van Tellingen, O., Beijnen, J. H., Wagenaar, E., van Deemter, L., Mol, C. A. A. M., van der Valk, M. A., Robanus-Maandag, E. C., te Riele, H. P. J., et al. (1994) · Cell · doi:10.1016/0092-8674(94)90212-7 · Cited by 2,281
Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)
Dhein, J., Walczak, H., Bäumler, C., Debatin, K.-M., & Krammer, P. H. (1995) · Nature · doi:10.1038/373438a0 · Cited by 1,609
Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation
Ju, S.-T., Panka, D. J., Cui, H., Ettinger, R., EI-Khatib, M., Sherr, D. H., Stanger, B. Z., & Marshak-Rothstein, A. (1995) · Nature · doi:10.1038/373444a0 · Cited by 1,499
Cited by
Death and anti-death: tumour resistance to apoptosis
Igney, F. H., & Krammer, P. H. (2002) · Nature Reviews Cancer · doi:10.1038/nrc776 · Cited by 2,075
ABC transporters in cancer: more than just drug efflux pumps
Fletcher, J. I., Haber, M., Henderson, M. J., & Norris, M. D. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2789 · Cited by 1,018
A side order of stem cells: the SP phenotype
Challen, G. A., & Little, M. H. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0116 · Cited by 475
Ishimoto, H., & Jaffe, R. B. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0001 · Cited by 379
Thévenod, F., Friedmann, J. M., Katsen, A. D., & Hauser, I. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.3.1887 · Cited by 301
Metadata
- Authors
- Smyth, M. J., Krasovskis, E., Sutton, V. R., & Johnstone, R. W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-06-09
- Volume
- 95
- Issue
- 12
- Pages
- 7024-7029
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2013995823
- Cited by
- 356
- References
- 43
- FWCI
- 8.30
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis. https://app.cochat.ai/papers/10.1073/pnas.95.12.7024
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- Smyth, M. J., Krasovskis, E., Sutton, V. R., & Johnstone, R. W. (1998). The drug efflux protein, P-glycoprotein, additionally protects drug-resistant tumor cells from multiple forms of caspase-dependent apoptosis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.95.12.7024
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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