Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers.

Abstract

Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers.

• Authors: Durray Shahwar, Muhammad Javed Iqbal, Mehr-Un Nisa, Milica Todorovska, Rukset Attar, Uteuliyev Yerzhan Sabitaliyevich, Ammad Ahmad Farooqi, Aamir Ahmad, Baojun Xu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 8 (Apr 24 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31022877 (Publication Type: Journal Article, Review)

Chemical References

• Biological Products
• Receptors, Death Domain
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNF-Related Apoptosis-Inducing Ligand

Topics

• Animals
• Apoptosis (drug effects)
• Biological Products (pharmacology)
• Humans
• Neoplasms (drug therapy, metabolism, pathology)
• Receptors, Death Domain (metabolism)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (metabolism)
• Signal Transduction (drug effects)
• TNF-Related Apoptosis-Inducing Ligand (metabolism)