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Amygdalin (vitamin B 17 ; previously called laetrile) is one of many nitrilosides, which are natural cyanide-containing substances abundant in the seeds of prunasin family, plant such as apricots, almonds, peaches, apples, and other rosaceous plants. Among the prunasins, Armeniacae semen has been used for the treatment of asthma, bronchitis, emphysema, leprosy, colorectal cancer, leucoderma, and pain. [1][2][3] Amygdalin is composed of two molecules of glucose, one of benzaldehyde, which induces an analgesic action, and one of hydrocyanic acid, which is an anti-neoplastic compound. Apart from the above indications, amygdalin has been used to treat cancers and relieve pain. [4][5][6] In particular, D-amygdalin (D-mandelonitrile-b-D-gentiobioside) is known to exhibit selective killing effect on cancer cells. 7)Prostate cancer is one of the most common non-skin cancers in men. This malignant tumor most often arises in the outer part of the prostate, and as the tumor grows it metastasizes to the tissues around the prostate or into the seminal vesicles. 8)Apoptosis, also known as programmed cell death, occurs in several pathological situations in multicellular organisms and constitutes part of a common mechanism of cell replacement, tissue remodeling, and removal of damaged cells. Apoptosis is a complex process characterized by cell shrinkage, chromatin condensation, internucleosomal DNA fragmentation, and formation of "apoptotic bodies." 9) Two important groups of proteins involved in apoptotic cell death are the members of the Bcl-2 family 10) and a class of cysteine proteases known as caspases.11) The Bcl-2 family can be classified into two functionally distinct groups: antiapoptotic proteins and pro-apoptotic proteins. Bcl-2, an antiapoptotic protein, is known to regulate apoptotic pathways and protects against cell death. Bax, a pro-apoptotic protein of that family, is expressed abundantly and selectively during apoptosis and promotes cell death. Increasing the ratio of Bcl-2 to Bax has commonly been used to determine the induction of apoptosis in several tissues.12) The caspases are aspartate-specific cysteine proteases that have emerged as the central executioner of apoptosis. Among the caspases, activation of caspase-3 is regarded as primary mechanism of apoptosis. 11,13) Caspase-3 can be activated through cytosolic release of cytochrome c by Bax protein. 14)Numerous studies have documented that induction of apoptosis is a very important mechanism in the spontaneous regression of tumors and in the development of anti-tumor agents.15) Apoptosis of tumor cells contributes to the tumor reduction and promotes tumor regression.16) Moreover, anticancer drugs are known to induce apoptosis of tumor cells by damaging their DNA, inhibiting DNA synthesis, depleting intracellular nucleotide pool, and disrupting mitotic apparatus. 17,18) In the present study, we prepared the aqueous extract of the amygdalin from Armeniacae semen and investigated whether this extract induces apoptotic cell death in human DU145 and LNCaP p...

Mast cells play an important role in tumorigenesis. Histamine released from mast cells stimulates new vessel formation by acting through the histamine1 (H1) receptor. Despite the evidence of the role of mast cells in tumor growth and angiogenesis, the potential mechanism remains to be elucidated. Therefore, we investigated the role of mast cell-derived HIF-1a in melanoma growth. Here, we identify that the most positive cells for HIF-1a staining are seen in mast cells of human and animal melanoma tissue. The number of the stromal cell types (fibroblasts, macrophages and endothelial cells) was also increased in melanoma tissues. In activated bone marrow-derived mast cells (BMMCs), expressions of HIF-1a and VEGF were increased. Histamine also induced the expressions of HIF-1a and VEGF in BMMCs. H1 receptor antagonists significantly improved overall survival rates and substantially suppressed tumor growth as well as the infiltration of mast cells and levels of VEGF through the inhibition of HIF-1a expression in B16F10 melanoma-bearing mice. Furthermore, the injection of HIF-1a depleted BMMCs markedly inhibited the growth of tumors and migration of mast cells and increased the survival rate of the mice. These findings emphasize that the growth of melanoma can actually be exacerbated by mast cell-derived HIF-1a. In aggregate, our results reveal a novel role for mast cell-derived HIF-1a in the melanoma microenvironment and have important implications for the design of therapeutic strategies.

IntroductionInterleukin (IL)-32 is an inflammatory cytokine induced by Mycobacterium tuberculosis and Mycobacterium bovis in a variety of cell types and discovered in the synovial of patients with rheumatoid arthritis (RA). Thymic stromal lymphopoietin (TSLP) play several roles in the pathogenesis of RA. However, the role of IL-32 and TSLP in RA has not been elucidated.MethodsWe evaluated the specific mechanism of between IL-32 and TSLP in RA using human monocyte cell line, THP-1 cells.ResultsHere we documented for the first time that IL-32 highly increased TSLP production in THP-1 cells and human blood monocytes. TSLP expression was induced by IL-32 via activation of caspase-1 and nuclear factor-κB. TSLP produced by IL-32 increased differentiation of monocytes but depletion of TSLP prevented differentiation of monocytes into macrophage-like cells. Chondroprotective drugs such as chondroitin sulfate (CS) and the traditional Korean medicine, BaekJeol-Tang (BT) decrease production of TSLP and activation of caspase-1 and nuclear factor-κB. In addition, CS and BT inhibited IL-32-induced monocytes differentiation.ConclusionsTaken together, IL-32 and TSLP are important cytokines involved in the development of RA. The effects of CS and BT were associated with the downregulation of TSLP and caspase-1 through negative regulation of IL-32 pathways in RA.

These results show that amygdalin exerts anti-inflammatory and analgesic effects and it dose so probably by suppressing the mRNA expressions of COX-2 and iNOS.

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The prevalence of allergic disease has been increasing over the past few decades in the majority of Western industrialized nations. There are some socioeconomic disparities regarding allergic disease status and management. Pyeongwee-San (KMP6) is Korean medicine for the treatment of gastrointestinal tract disease. It is known that KMP6 has an improving effect on the spleen and stomach functions in traditional Korean medical theory. Here, we hypothesized that KMP6 could be used to regulate the inflammatory reaction. We show the molecular mechanisms of Pyeongwee-San (KMP6) on inflammatory reactions. A molecular docking simulation showed that hesperidin, component of KMP6, regulate the enzymatic activity by interaction in the active site of caspase-1. KMP6 control the activity of caspase-1 in activated human mast cell line (HMC-1 cells). KMP6 reduced the expression of receptor interacting protein (RIP)-2 in HMC-1 cells. Thymic stromal lymphopoietin protein production and mRNA expression were inhibited by KMP6. In the activated HMC-1 cells, KMP6 suppressed the activation of mitogen-ativated protein kinase and nuclear factor-kappaB. In addition, KMP6 significantly inhibited the expression of inflammatory cytokines. Our findings indicate that KMP6 may attenuate allergic reactions via the regulation of caspase-1/RIP-2 signaling pathway. These studies will help advance the social welfare system.

BiRyuChe-bang (BRC) is a Korean prescription medicine, which has been used to treat allergic rhinitis at Kyung Hee Medical Center. In this work, we investigated the effects of BRC on mast cell-mediated allergic reactions and inflammatory cytokines production, and identified the active component of BRC. Histamine release was measured from rat peritoneal mast cells (RPMCs). Ear swelling and passive cutaneous anaphylaxis (PCA) were examined in mouse models. Phorbol 12-myristate 13-acetate (PMA) plus A23187-induced inflammatory cytokines production was measured using enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used for the expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8. Activation of nuclear factor (NF)-κB was analyzed by Western blotting. BRC significantly inhibited the compound 48/80-induced ear swelling response, histamine release from RPMCs, PCA activated by anti-dinitrophenyl IgE, and PMA plus A23187-induced inflammatory cytokines production (p < 0.05). In addition, BRC dose-dependently inhibited the mRNA expressions of TNF-α, IL-6, and IL-8 as well as the activation of NF-κB in a human mast cell line, HMC-1 cells. BRC inhibited the levels of TNF-α and IL-6 in mice induced with PCA. Several components of BRC, such as 1,8-Cineole, Linalool, Linalyl acetate, α-Pinene, and α-Terpineol, significantly inhibited the release of histamine from RPMCs (p < 0.05). Among these components, Linalyl acetate was the most effective for inhibiting histamine release. These results indicate that BRC has a potential regulatory effect on allergic and inflammatory reactions mediated by mast cells.