title: Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy.
abstract: 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.
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors: Xiaoyun
authors: X
authors: Dai
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors: Jingwen
authors: J
authors: Zhang
authors: School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Western Australia 6009, Australia.
authors: Frank
authors: F
authors: Arfuso
authors: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
authors: Arunachalam
authors: A
authors: Chinnathambi
authors: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
authors: M E
authors: ME
authors: Zayed
authors: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
authors: Sulaiman Ali
authors: SA
authors: Alharbi
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Western Australia 6009, Australia Cancer Science Institute of Singapore, Centre for Translational Medicine, Singapore 117599, Singapore Department of Biological Sciences, University of North Texas, Denton, TX 76203, USA.
authors: Alan Prem
authors: AP
authors: Kumar
authors: College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea phcgs@nus.edu.sg ksahn@khu.ac.kr.
authors: Kwang Seok
authors: KS
authors: Ahn
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore School of Biomedical Sciences, CHIRI Biosciences Research Precinct, Curtin University, Western Australia 6009, Australia Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia phcgs@nus.edu.sg ksahn@khu.ac.kr.
authors: Gautam
authors: G
authors: Sethi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D016328:NF-kappa B; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: NF-κB; TRAIL; apoptosis; cancer; natural products