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alpha-TEA inhibits survival and enhances death pathways in cisplatin sensitive and resistant human ovarian cancer cells.
Apoptosis. 2006 Oct; 11(10):1813-23.A

Abstract

RRR-alpha-tocopherol ether linked acetic acid analog (alpha-TEA), is a potential chemotherapeutic agent for ovarian cancer. Pro-death and pro-life signaling pathways were studied to understand the anti-cancer actions of alpha-TEA on cisplatin-sensitive (A2780S) and -resistant (A2780/cp70R) human ovarian cancer cells. Both cell lines were refractory to Fas; whereas, alpha-TEA sensitized them to Fas signaling. alpha-TEA increased levels of Fas message, protein and membrane-associated Fas. Neutralizing antibodies to Fas or Fas L partially blocked alpha-TEA-induced apoptosis. alpha-TEA induced prolonged activation of c-Jun N-terminal kinase (JNK) and its substrate c-Jun; Bax conformational change; and cleavage of Bid and caspases-8, -9 and -3. Chemical inhibitors of JNK, and caspases blocked alpha-TEA-induced apoptosis. alpha-TEA decreased phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK1/2), as well as cellular FLICE-like inhibitory protein (c-FLIP) and Survivin protein levels. Knockdown of Akt and ERK activity using phosphoinositide- 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MKK1) inhibitors enhanced alpha-TEA-induced apoptosis. Over-expression of constitutively active Akt2 and MKK1 blocked alpha-TEA-induced apoptosis. Collectively, data show alpha-TEA to be a potent apoptotic inducer of both cisplatin-sensitive and -resistant human ovarian cancer cells via activating death receptor Fas signaling and suppressing anti-apoptotic AKT and ERK targets.

Authors+Show Affiliations

School of Biological Sciences/C0900, University of Texas at Austin, 78712, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16850165

Citation

Yu, Weiping, et al. "Alpha-TEA Inhibits Survival and Enhances Death Pathways in Cisplatin Sensitive and Resistant Human Ovarian Cancer Cells." Apoptosis : an International Journal On Programmed Cell Death, vol. 11, no. 10, 2006, pp. 1813-23.
Yu W, Shun MC, Anderson K, et al. Alpha-TEA inhibits survival and enhances death pathways in cisplatin sensitive and resistant human ovarian cancer cells. Apoptosis. 2006;11(10):1813-23.
Yu, W., Shun, M. C., Anderson, K., Chen, H., Sanders, B. G., & Kline, K. (2006). Alpha-TEA inhibits survival and enhances death pathways in cisplatin sensitive and resistant human ovarian cancer cells. Apoptosis : an International Journal On Programmed Cell Death, 11(10), 1813-23.
Yu W, et al. Alpha-TEA Inhibits Survival and Enhances Death Pathways in Cisplatin Sensitive and Resistant Human Ovarian Cancer Cells. Apoptosis. 2006;11(10):1813-23. PubMed PMID: 16850165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - alpha-TEA inhibits survival and enhances death pathways in cisplatin sensitive and resistant human ovarian cancer cells. AU - Yu,Weiping, AU - Shun,Ming-chieh, AU - Anderson,Kristen, AU - Chen,Hansong, AU - Sanders,Bob G, AU - Kline,Kimberly, PY - 2006/7/20/pubmed PY - 2006/12/9/medline PY - 2006/7/20/entrez SP - 1813 EP - 23 JF - Apoptosis : an international journal on programmed cell death JO - Apoptosis VL - 11 IS - 10 N2 - RRR-alpha-tocopherol ether linked acetic acid analog (alpha-TEA), is a potential chemotherapeutic agent for ovarian cancer. Pro-death and pro-life signaling pathways were studied to understand the anti-cancer actions of alpha-TEA on cisplatin-sensitive (A2780S) and -resistant (A2780/cp70R) human ovarian cancer cells. Both cell lines were refractory to Fas; whereas, alpha-TEA sensitized them to Fas signaling. alpha-TEA increased levels of Fas message, protein and membrane-associated Fas. Neutralizing antibodies to Fas or Fas L partially blocked alpha-TEA-induced apoptosis. alpha-TEA induced prolonged activation of c-Jun N-terminal kinase (JNK) and its substrate c-Jun; Bax conformational change; and cleavage of Bid and caspases-8, -9 and -3. Chemical inhibitors of JNK, and caspases blocked alpha-TEA-induced apoptosis. alpha-TEA decreased phosphorylation of protein kinase B (Akt/PKB) and extracellular signal-regulated kinase (ERK1/2), as well as cellular FLICE-like inhibitory protein (c-FLIP) and Survivin protein levels. Knockdown of Akt and ERK activity using phosphoinositide- 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MKK1) inhibitors enhanced alpha-TEA-induced apoptosis. Over-expression of constitutively active Akt2 and MKK1 blocked alpha-TEA-induced apoptosis. Collectively, data show alpha-TEA to be a potent apoptotic inducer of both cisplatin-sensitive and -resistant human ovarian cancer cells via activating death receptor Fas signaling and suppressing anti-apoptotic AKT and ERK targets. SN - 1360-8185 UR - https://www.unboundmedicine.com/medline/citation/16850165/alpha_TEA_inhibits_survival_and_enhances_death_pathways_in_cisplatin_sensitive_and_resistant_human_ovarian_cancer_cells_ L2 - https://doi.org/10.1007/s10495-006-9234-5 DB - PRIME DP - Unbound Medicine ER -