Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra

摘要

Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) is a type II membrane protein belonged to Tumor Necrosis Factor (TNF) family acting as mediator of the immune system and the inflammatory response, and inducing apoptosis in some cell types [1]. There is a progressive expansion in the proteome involved in TRAIL-mediated apoptosis due to its death induction selectively in cancer cells [2-6]. Potential of TRAIL in inducing apoptosis in cancer cells was a major breakthrough in molecular oncology [2-4]. It is noted that the death receptors, which are members of the TNF receptor superfamily, trigger apoptotic signaling via TRAIL to induce apoptotic death in cancer cells [5, 7, 8]. Upon apoptosis stimuli, the death-inducing signaling complex (DISC) is formed [5, 8]. DISC is composed of the various death receptors, an adaptor protein that bridges members of the TNF receptor superfamily (TNFRSF), Fas-associated protein with death domain (FADD), and caspase-8, as reviewed in [5, 8]. DISC acts as protein assembly platform for recruitment of caspase-8 while transducing a downstream signal cascade resulting in apoptosis [5, 8]. Rapidly accumulating data suggests that TRAIL-mediated signals can be transduced within a cell through two distinct molecular signaling pathways, such as extrinsic (receptor-mediated) and intrinsic (mitochondrial) pathways [5]. Both pathways are essentially leading to activation of caspase cascade pathway [5, 7, 8]. Biologically, caspases are categorized into two initiator caspases and executioner caspases [5].In the upcoming sections, we will give an overview of how TRAIL-induced signals intracellularly trigger apoptosis starting from an exploration of TRAIL-mediated signaling pathway and its regulation. We will further discuss the bioactive ingredients, which have shown a potential treatment use in targeting protein network to restore TRAIL-mediated apoptosis in resistant cancer cells. We finally discuss potential effects of natural phytometabolites on the cancer cell survival and the TRAIL-mediated pathway as a potential anticancer therapeutic approach.