期刊
EXPERIMENTAL BIOLOGY AND MEDICINE
卷 240, 期 6, 页码 760-773出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1535370215579167
关键词
TRAIL; cancer; NF-kappa B; apoptosis; natural products
资金
- NUHS Bench to Bedside to Product grant
- Deanship of Scientific Research, College of Science Research Centre, King Saud University, Kingdom of Saudi Arabia
- Korea Science and Engineering Foundation (KOSEF) grant - Korean Ministry of Education, Science and Technology (MoEST) [2011-0006220]
- Singapore Ministry of Education Tier 2 [MOE2012-T2-2-139]
- NUHS Bench-to-Bedside-To-Product [R-184-000-243-515]
- Cancer Science Institute of Singapore, Experimental Therapeutics I Program [R-713-001-011-271]
- National Research Foundation of Korea [2007-0054931] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to selectively induce apoptotic cell death in various tumor cells by engaging its death-inducing receptors (TRAIL-R1 and TRAIL-R2). This property has led to the development of a number of TRAIL-receptor agonists such as the soluble recombinant TRAIL and agonistic antibodies, which have shown promising anticancer activity in preclinical studies. However, besides activating caspase-dependent apoptosis in several cancer cells, TRAIL may also activate nonapoptotic signal transduction pathways such as nuclear factor-kappa B, mitogen-activated protein kinases, AKT, and signal transducers and activators of transcription 3, which may contribute to TRAIL resistance that is being now frequently encountered in various cancers. TRAIL resistance can be overcome by the application of efficient TRAIL-sensitizing pharmacological agents. Natural compounds have shown a great potential in sensitizing cells to TRAIL treatment through suppression of distinct survival pathways. In this review, we have summarized both apoptotic and nonapoptotic pathways activated by TRAIL, as well as recent advances in developing TRAIL-receptor agonists for cancer therapy. We also briefly discuss combination therapies that have shown great potential in overcoming TRAIL resistance in various tumors.
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