The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Induction of cancer cell apoptosis by α‐tocopheryl succinate: molecular pathways and structural requirements
Abstract
The vitamin E analog α‐tocopheryl succinate (α‐TOS) can induce apoptosis. We show that the proapoptotic activity of α‐TOS in hematopoietic and cancer cell lines involves inhibition of protein kinase C (PKC), since phorbol myristyl acetate prevented α‐TOS‐triggered apoptosis. More selective effectors indicated that α‐TOS reduced PKCα isotype activity by increasing protein phosphatase 2A (PP2A) activity. The role of PKCα inhibition in α‐TOS‐induced apoptosis was confirmed using antisense oligonucleotides or PKCα overexpression. Gain‐ or loss‐of‐function bcl‐2 mutants implied modulation of bcl‐2 activity by PKC/ PP2A as a mitochondrial target of α‐TOS‐induced proapoptotic signals. Structural analogs revealed that α‐tocopheryl and succinyl moieties are both required for maximizing these effects. In mice with colon cancer xenografts, α‐TOS suppressed tumor growth by 80%. This epitomizes cancer cell killing by a pharmacologically relevant compound without known side effects.—Neuzil, J., Weber, T., Schröder, A., Lu, M., Ostermann, G., Gellert, N., Mayne, G. C., Olejnicka, B., Nègre‐Salvayre, A., Stícha, M., Coffey, R. J., Weber, C. Induction of cancer cell apoptosis by α‐tocopheryl succinate: molecular pathways and structural requirements. FASEB J. 15, 403‐415 (2001)
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Protein phosphatase 2A: a target for anticancer therapy
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Metadata
- Authors
- NEUZIL, J., WEBER, T., SCHRÖDER, A., LU, M., OSTERMANN, G., GELLERT, N., MAYNE, G. C., OLEJNICKA, B., NÈGRE‐SALVAYRE, A., STÍCHA, M., COFFEY, R. J., & WEBER, C.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2001-02
- Volume
- 15
- Issue
- 2
- Pages
- 403-415
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2100914972
- Cited by
- 287
- References
- 53
- FWCI
- 8.69
- Type
- journal article
- Language
- en
- Open access
- closed
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- NEUZIL, J., WEBER, T., SCHRÖDER, A., LU, M., OSTERMANN, G., GELLERT, N., MAYNE, G. C., OLEJNICKA, B., NÈGRE‐SALVAYRE, A., STÍCHA, M., COFFEY, R. J., & WEBER, C. (2001). Induction of cancer cell apoptosis by α‐tocopheryl succinate: molecular pathways and structural requirements. The FASEB Journal. https://doi.org/10.1096/fj.00-0251com
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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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