Vitamin E δ-tocotrienol sensitizes human pancreatic cancer cells to TRAIL-induced apoptosis through proteasome-mediated down-regulation of c-FLIPs

Cancer Cell International
Rony A FrancoisMokenge P Malafa

Abstract

Vitamin E δ-tocotrienol (VEDT), a vitamin E compound isolated from sources such as palm fruit and annatto beans, has been reported to have cancer chemopreventive and therapeutic effects. We report a novel function of VEDT in augmenting tumor necrosis factor-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis in pancreatic cancer cells. The effects of VEDT were shown by its ability to trigger caspase-8-dependent apoptosis in pancreatic cancer cells. When combined with TRAIL, VEDT significantly augmented TRAIL-induced apoptosis of pancreatic cancer cells. VEDT decreased cellular FLICE inhibitory protein (c-FLIP) levels without consistently modulating the expression of decoy death receptors 1, 2, 3 or death receptors 4 and 5. Enforced expression of c-FLIP substantially attenuated VEDT/TRAIL-induced apoptosis. Thus, c-FLIP reduction plays an important part in mediating VEDT/TRAIL-induced apoptosis. Moreover, VEDT increased c-FLIP ubiquitination and degradation but did not affect its transcription, suggesting that VEDT decreases c-FLIP levels through promoting its degradation. Of note, degradation of c-FLIP and enhanced TRAIL-induced apoptosis in pancreatic cancer cells were observed only with the anticancer bioactive vita...Continue Reading

References

Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
Apr 14, 1999·Cell Death and Differentiation·A G Porter, R U Jänicke
Feb 26, 2000·Carcinogenesis·S W Lowe, A W Lin
Nov 20, 2001·Molecular and Cellular Biology·A KruegerS Kirchhoff
Jun 2, 2006·Journal of the American Society of Nephrology : JASN·Stewart H LeckerWilliam E Mitch
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
May 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jong W YuYigong Shi
Aug 26, 2009·Journal of Agricultural and Food Chemistry·Akira ShibataTeruo Miyazawa
Aug 11, 2010·Biochemical Pharmacology·Bharat B AggarwalRamaswamy Kannappan
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
May 19, 2011·Genes & Nutrition·Bharat Aggarwal, Kalanithi Nesaretnam
Jun 16, 2011·International Journal of Molecular Sciences·Tao YinChunyou Wang
Jul 23, 2011·Current Pharmaceutical Design·Z Q HuangD J Buchsbaum
Nov 19, 2011·Carcinogenesis·Ming T LingKum K Khanna
Jul 9, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kaiyu YuanYabing Chen
Nov 10, 2013·Journal of the National Cancer Institute·Jiemin MaAhmedin Jemal
Jan 9, 2014·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Aug 16, 2016·Cell Research·Minghui GaoXuejun Jiang
Nov 20, 2016·Journal of Cellular and Molecular Medicine·Haitao YuGang Chen
Apr 5, 2017·Journal of the National Cancer Institute·Ahmedin JemalHannah K Weir

❮ Previous
Next ❯

Citations

Aug 4, 2021·Cancer Metastasis Reviews·Nianhong ChenPing Shi

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
transfections
immunoprecipitation
PCR
xenograft
xenografts
transfection
ubiquitination
co-immunoprecipitation

Software Mentioned

FLOW
GraphPad Prism
JO
SAS
AlphaEaseFC

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis