Effect of Natural Compounds on NK Cell Activation

Abstract

Natural killer (NK) cells are lymphocytes of the innate immune system that survey the body for stressed and abnormal cells. The integration of signals that they receive through various inhibitory and activating cell surface receptors controls their activation and ability to kill target cells and produce cytokines. In this manner, phenotypically and functionally distinct subsets of NK cells help protect against microbial infections and cancer and shape the adaptive immune response. NK cells can use two different mechanisms to kill their targets, either by cytotoxic granule exocytosis or by induction of death receptor-mediated apoptosis. Death ligands belong to the tumor necrosis factor (TNF) family of ligands. Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell through which granzymes and associated molecules can enter and induce apoptosis. NK cells are also involved in antibody-dependent cellular toxicity via the CD16 receptor. In addition to target recognition, NK cells can be also activated by treatment with multiple compounds with stimulatory properties. Apart from interleukins, which belong to the best characterized group of NK cell-stimulating compounds, vitamins and constituents extracted from plants also display the ability to activate NK cells. The current review characterizes several groups of NK cell-activating compounds: vitamins belonging to classes A, B, C, D, and E, polysaccharides, lectins, and a number of phytochemicals used in cancer research, exhibiting stimulatory properties when applied to NK cells. Although in most cases the exact mechanism of action is not known, constituents described in this review seem to be promising candidates for NK cell-stimulating drugs.

Allium vegetables for possible future of cancer treatment

“…A study by the Chinese Academy of Medical Sciences found that there was an inverse relationship between the consumption of garlic and the incidence of gastric cancer (Li, Ying, Shan, & Ji, ). Garlic prevents the growth of cancer by increasing the activity of natural killer (NK) cells and macrophages (Grudzien & Rapak, ). The results of a study published in the American Society for Nutrition Journal showed that although aged garlic extract did not improve the quality of life, it improved the activity of NK cells in patients with advanced gastrointestinal cancer (Ishikawa et al, ).…”

“…Garlic prevents the growth of cancer by increasing the activity of natural killer (NK) cells and macrophages (Grudzien & Rapak, 2018). The results of a study published in the American Society for Nutrition Journal showed that although aged garlic extract did not improve the quality of life, it improved the activity of NK cells in patients with advanced gastrointestinal cancer (Ishikawa et al, 2006).…”

“…For many years, they have been used to prevent and treat certain diseases such as diabetes, arthritis, colds and flu, cough, headache, hemorrhage, asthma, atherosclerosis, and inflammatory diseases (H. A. R. Suleria, Butt, Anjum, Arshad, & Khalid, 2013;Zeng et al, 2017). It has recently been noted that these vegetables, in addition to the conventional antibacterial, antifungal, antiviral, antiprotozoal, and antiworm effects, showed extensive in vitro and in vivo antiproliferative, antimotility, and cytotoxic potentials against cancer cells (Abdelrahman, Mahmoud, El-Sayed, Tanaka, & Tran, 2017; Chu et al, -Others antitumor effects (chelating irons, ↓p38 adhesion of tumor cells and metastasis, growth inhibition, cell cycle arrest, ↑ROS production and damaging to lipids and proteins, ↓MMP, antiangiogenesis, block cellular aging, hindering cellular division by expression of p38, ↓autophagy, ↓side effects of chemotherapy and radiotherapy, AMPK/ TSC2 expression and beclin-1 signaling pathways) (Thomson & Ali, 2003), (Saedi, Md Noor, Ismail, & Othman, 2014), (Oommen, Anto, Srinivas, & Karunagaran, 2004) (Grudzien & Rapak, 2018), (Ishikawa et al, 2006), (Lestari & Rifa'i, 2018) (Saud et al, 2016;Ziaei et al, 2015), (Hodge, Hodge, & Han, 2002), (Guan, Zhao, Xie, & Zeng, 2018) (Belloir, Singh, Daurat, Siess, & Le Bon, 2006), (Knowles & Milner, 2003) (De Martino, Filomeni, Aquilano, Ciriolo, & Rotilio, 2006), (DeLeon, Gao, Huang, & Olson, 2016;Ueda et al, 2002), (Y.-L. Chu et al, 2013) (Belloir et al, 2006), (Yamazaki et al, 1992) (Saud et al, 2016;Ziaei et al, 2015), (Hodge et al, 2002) , (H.-S. Chang et al, 2012), (Sowjanya, Devi, & Madhavi, 2009;Upadhyay, 2017), (Lin et al, 2017), (Y.-L. …”

Non-Genetically Improving the Natural Cytotoxicity of Natural Killer (NK) Cells

“…Several vitamins, e.g., A, C, and E, induce changes in NK cell markers associated to activation (60). Vitamin A/retinoic acid increases target expression of natural-killer group 2, member D (NKG2D) ligands in mouse, RAE-1 (60), and humans, MICA/B (61,62).…”

“…Vitamin A/retinoic acid increases target expression of natural-killer group 2, member D (NKG2D) ligands in mouse, RAE-1 (60), and humans, MICA/B (61,62). However, it can activate (60,62) or inhibit (14,60,63) NK activity depending on the cellular context. Hence, their use in clinics must be carefully studied.…”