Gomisin G Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing AKT Phosphorylation and Decreasing Cyclin D1

Maharjan, Sony; Kim, Dongbum; Lee, Su-In; Lim, Yoonho; Lee, Keunwook; Kwon, Hyung‐Joo

doi:10.4062/biomolther.2017.235

Cited by 14 publications

(16 citation statements)

References 34 publications

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“…Dextran sodium sulfate was purchased from Sigma-Aldrich (MO, USA). The chemical compounds of A. gigas were provided by Yoongho Lim (Konkuk University, Seoul, Korea): twelve active ingredients of A. gigas was purchased from Biopurify Phytochemicals Ltd (Sichuan, China) and the purity of each compound was at least 98% as determined by HPLC system fitted with a RP-C18 column (Phenomenex, Torrance, CA, USA) (Maharjan et al ., 2018). Fluorophore conjugated antibodies against CD4, CD11b, Gr-1 and IFN-γ; the neutralizing antibodies against IL-4, IL-12 and IFN-γ; the antibody against CD3ε and CD28 were purchased from BD biosciences (CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Decursinol Angelate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Modulating Type 17 Helper T Cell Responses

Thapa

Pak

Kwon

et al. 2019

Biomolecules & Therapeutics

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Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.

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Section: Methodsmentioning

confidence: 99%

Decursinol Angelate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Modulating Type 17 Helper T Cell Responses

Thapa

Pak

Kwon

et al. 2019

Biomolecules & Therapeutics

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“…Considering the fact that gomisin J induces autophagy-mediated cell death, which is promoted by the inhibition of mTOR, we assumed that the PI3K/AKT/mTOR pathway could be influenced by gomisin J (30)(31)(32)(33), which needs to be investigated in the future. In fact, Maharjan et al proposed that gomisin G, a related compound of gomisin J, blocked the AKT pathway that is upstream of mTOR (34). As gomisin J can enhance the efficacy of anticancer drugs through the induction of two types of PCD in cancer cells, our next project is to study this mechanism and to identify the involved regulatory proteins or pathways.…”

Section: Discussionmentioning

confidence: 99%

Anticancer activity of gomisin�J from Schisandra chinensis fruit

et al. 2018

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In attempting to identify effective anticancer drugs from natural products that are harmless to humans, we found that the gomisin J from Schisandra chinensis fruit has anticancer activity. Schisandra chinensis fruits are used in traditional herbal medicine and gomisin J is one of their chemical constituents. In the present study, we examined the anticancer activity of gomisin J in MCF7 and MDA-MB-231 breast cancer cell lines and in MCF10A normal cell line, in a time-and concentration-dependent manner. Our data revealed that gomisin J exerted a much stronger cytotoxic effect on MCF7 and MDA-MB-231 cancer cells than on MCF10A normal cells. Gomisin J suppressed the proliferation and decreased the viability of MCF7 and MDA-MB-231 cells at relatively low (<10 µg/ml) and high (>30 µg/ml) concentrations, respectively. Our data also revealed that gomisin J induced necroptosis, a programmed form of necrosis, as well as apoptosis. Notably, gomisin J predominantly induced necroptosis in MCF7 cells that are known to have high resistance to many pro-apoptotic anticancer drugs, while MDA-MB-231 exhibited a much lower level of necroptosis but instead a higher level of apoptosis. This data indicated the possibility that it may be used as a more effective anticancer drug, especially in apoptosis-resistant malignant cancer cells. In an extended study, gomisin J exhibited a strong cytotoxic effect on all tested various types of 13 cancer cell lines, indicating its potential to be used against a wide range of different types of cancer cells.

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“…MERS-CoV-infected Vero cell lysates were run on SDS-PAGE and subsequently transferred onto a nitrocellulose membrane as described previously (26, 27), and detailed information is provided in the Supplementary Material.…”

Section: Methodsmentioning

confidence: 99%

Generation and characterization of a monoclonal antibody against MERS-CoV targeting the spike protein using a synthetic peptide epitope-CpG-DNA-liposome complex

et al. 2019

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Middle East respiratory syndrome coronavirus (MERS-CoV) uses the spike (S) glycoprotein to recognize and enter target cells. In this study, we selected two epitope peptide sequences within the receptor binding domain (RBD) of the MERS-CoV S protein. We used a complex consisting of the epitope peptide of the MERS-CoV S protein and CpG-DNA encapsulated in liposome complex to immunize mice, and produced the monoclonal antibodies 506-2G10G5 and 492-1G10E4E2. The western blotting data showed that both monoclonal antibodies detected the S protein and immunoprecipitated the native form of the S protein. Indirect immunofluorescence and confocal analysis suggested strong reactivity of the antibodies towards the S protein of MERS-CoV virus infected Vero cells. Furthermore, the 506-2G10G5 monoclonal antibody significantly reduced plaque formation in MERS-CoV infected Vero cells compared to normal mouse IgG and 492-1G10E4E2. Thus, we successfully produced a monoclonal antibody directed against the RBD domain of the S protein which could be used in the development of diagnostics and therapeutic applications in the future.

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Gomisin G Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing AKT Phosphorylation and Decreasing Cyclin D1

Cited by 14 publications

References 34 publications

Decursinol Angelate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Modulating Type 17 Helper T Cell Responses

Decursinol Angelate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Modulating Type 17 Helper T Cell Responses

Anticancer activity of gomisin�J from Schisandra chinensis fruit

Generation and characterization of a monoclonal antibody against MERS-CoV targeting the spike protein using a synthetic peptide epitope-CpG-DNA-liposome complex

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