Anti-cancer activity of Angelica gigas by increasing immune response and stimulating natural killer and natural killer T cells

Abstract

BackgroundThe polysaccharide component of Angelica gigas induces immuno-stimulatory effects on innate immune cells. However, it is unclear whether A. gigas’ adjuvant activity on the immune system can elicit anti-cancer responses.MethodsA water-soluble immuno-stimulatory component of A. gigas was prepared. How this ISAg modulated the activation of innate immune cells such as dendritic cells (DCs) was examined. ISAg-induced cytotoxic activity via natural killer (NK) and NKT cells was also tested using a tumor-bearing mouse model.ResultsISAg treatment induced nitric oxide (NO) production and cytokine gene expression involved in innate immune responses. ISAg activated macrophages and DCs to secrete cytokine IL-12, through the TLR4 signaling pathway. IL-12 plays a crucial role in ISAg-mediated NK and NKT cell activation. Thus, the anti-cancer activity of NK and NKT cells induced ISAg-mediated cytotoxicity of B16 melanoma cells in mice.ConclusionsThese results indicated that the natural ingredient, ISAg, has adjuvant activity to induce strong anti-cancer activity of NK and NKT cells in vivo.

Effects of Decursin and Angelica gigas Nakai Root Extract on Hair Growth in Mouse Dorsal Skin via Regulating Inflammatory Cytokines

“…Angelica gigas Nakai (AGN) belongs to the Umbelliferae family and has been traditionally used in oriental remedies due to its many advantageous attributes, such as antiepileptic, hepatoprotective, anti-cancer, anti-inflammatory, and anti-amnesic activities [12][13][14][15][16][17]. Concerning the case of hair growth using AGN, the extract of the roots of AGN is frequently included as a hair growth-facilitating component in combined herbal extracts [18][19][20][21].…”

TLR4-dependent effects of ISAg treatment on conventional T cell polarization in vivo

“…Recently, we demonstrated that the water-soluble polysaccharide fraction of A. gigas , ISAg, elicits anticancer effects through cytotoxic activity of NK and NKT cells (Kim et al. 2018b). Since it is well established that the overproduction of IL12p40 by DCs leads to Th1 polarization of conventional CD4 + and CD8 + T cells (Mayordomo et al.…”

“…We previously showed that ISAg-mediated IL12 production by DCs and macrophages is dependent on the TLR4 pathway (Kim et al. 2018b). However, since it was reported that TLR2 and TLR4 ligands directly activate NK and NKT cells (Martinez et al.…”

“…ISAg was isolated from A. gigas Nakai roots, as described previously (Kim et al. 2018b). LPS was obtained from Sigma-Aldrich (St. Louis, MO, USA).…”

“…Recently, we demonstrated that the immuno-stimulatory fraction of A. gigas (ISAg), which is composed of water-soluble polysaccharides, elicits anticancer effects via the activation of NK and NKT cells, which are known to play important roles in innate immune responses (Kim et al. 2018b). Thus, in this study, we investigated whether ISAg influences the activation and polarization of conventional T cells such as CD4 + and CD8 + T cells in vivo .…”