The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Requirement for ERK Activation in Cisplatin-induced Apoptosis
Open accessAbstract
Cisplatin activates multiple signal transduction pathways involved in coordinating cellular responses to stress. Here we demonstrate a requirement for extracellular signal-regulated protein kinase (ERK), a member of the mitogen-activated protein kinase family in mediating cisplatin-induced apoptosis of human cervical carcinoma HeLa cells. Cisplatin treatment resulted in dose- and time- dependent activation of ERK. That elevated ERK activity contributed to cell death by cisplatin was supported by several observations: 1) PD98059 and U0126, chemical inhibitors of the MEK/ERK signaling pathway, prevented apoptosis; 2) pretreatment of cells with TPA, an activator of the ERK pathway, enhanced their sensitivity to cisplatin; 3) suramin, a growth factor receptor antagonist that greatly suppressed ERK activation, likewise inhibited cisplatin-induced apoptosis; and, finally, 4) HeLa cell variants selected for cisplatin resistance showed reduced activation of ERK following cisplatin treatment. Cisplatin-induced apoptosis was associated with cytochrome c release and subsequent caspase-3 activation, both of which could be prevented by treatment with the MEK inhibitors. However, the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone protected HeLa cells against apoptosis without affecting ERK activation. Taken together, our findings suggest that ERK activation plays an active role in mediating cisplatin-induced apoptosis of HeLa cells and functions upstream of caspase activation to initiate the apoptotic signal.
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Self-citationOpposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis
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Self-citationIdentification of a Novel Inhibitor of Mitogen-activated Protein Kinase Kinase
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An APAF-1·Cytochrome c Multimeric Complex Is a Functional Apoptosome That Activates Procaspase-9
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Cited by
Cisplatin in cancer therapy: Molecular mechanisms of action
Dasari, S., & Bernard Tchounwou, P. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.07.025 · Cited by 5,537
Cellular processing of platinum anticancer drugs
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Cisplatin: mode of cytotoxic action and molecular basis of resistance
Siddik, Z. H. (2003) · Oncogene · doi:10.1038/sj.onc.1206933 · Cited by 3,335
Molecular mechanisms of cisplatin resistance
Galluzzi, L., Senovilla, L., Vitale, I., Michels, J., Martins, I., Kepp, O., Castedo, M., & Kroemer, G. (2012) · Oncogene · doi:10.1038/onc.2011.384 · Cited by 2,760
Cellular response to oxidative stress: Signaling for suicide and survival*
Martindale, J. L., & Holbrook, N. J. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10119 · Cited by 2,297
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Metadata
- Authors
- Wang, X., Martindale, J. L., & Holbrook, N. J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-12
- Volume
- 275
- Issue
- 50
- Pages
- 39435-39443
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2021736277
- Cited by
- 675
- References
- 51
- FWCI
- 8.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
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