Browsing by Subject "Peptide"

Now showing 1 - 5 of 5
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    Anticancer Peptides Derived from Aldolase A and Induced Tumor-Suppressing Cells Inhibit Pancreatic Ductal Adenocarcinoma Cells
    (MDPI, 2023-10-11) Cui, Changpeng; Huo, Qingji; Xiong, Xue; Li, Kexin; Fishel, Melissa L.; Li, Baiyan; Yokota, Hiroki; Biomedical Engineering, School of Engineering and Technology
    PDAC (pancreatic ductal adenocarcinoma) is a highly aggressive malignant tumor. We have previously developed induced tumor-suppressing cells (iTSCs) that secrete a group of tumor-suppressing proteins. Here, we examined a unique procedure to identify anticancer peptides (ACPs), using trypsin-digested iTSCs-derived protein fragments. Among the 10 ACP candidates, P04 (IGEHTPSALAIMENANVLAR) presented the most efficient anti-PDAC activities. P04 was derived from aldolase A (ALDOA), a glycolytic enzyme. Extracellular ALDOA, as well as P04, was predicted to interact with epidermal growth factor receptor (EGFR), and P04 downregulated oncoproteins such as Snail and Src. Importantly, P04 has no inhibitory effect on mesenchymal stem cells (MSCs). We also generated iTSCs by overexpressing ALDOA in MSCs and peripheral blood mononuclear cells (PBMCs). iTSC-derived conditioned medium (CM) inhibited the progression of PDAC cells as well as PDAC tissue fragments. The inhibitory effect of P04 was additive to that of CM and chemotherapeutic drugs such as 5-Flu and gemcitabine. Notably, applying mechanical vibration to PBMCs elevated ALDOA and converted PBMCs into iTSCs. Collectively, this study presented a unique procedure for selecting anticancer P04 from ALDOA in an iTSCs-derived proteome for the treatment of PDAC.
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    Anticancer peptides from induced tumor-suppressing cells for inhibiting osteosarcoma cells
    (e-Century, 2023-09-15) Cui, Chang-Peng; Huo, Qing-Ji; Xiong, Xue; Li, Ke-Xin; Ma, Peng; Qiang, Gui-Fen; Pandya, Pankita H.; Saadatzadeh, Mohammad R.; Vishehsaraei, Khadijeh Bijangi; Kacena, Melissa A.; Aryal, Uma K.; Pollok, Karen E.; Li, Bai-Yan; Yokota, Hiroki; Biomedical Engineering, School of Engineering and Technology
    Osteosarcoma (OS) is the most frequent primary bone cancer, which is mainly suffered by children and young adults. While the current surgical treatment combined with chemotherapy is effective for the early stage of OS, advanced OS preferentially metastasizes to the lung and is difficult to treat. Here, we examined the efficacy of ten anti-OS peptide candidates from a trypsin-digested conditioned medium that was derived from the secretome of induced tumor-suppressing cells (iTSCs). Using OS cell lines, the antitumor capabilities of the peptide candidates were evaluated by assaying the alterations in metabolic activities, proliferation, motility, and invasion of OS cells. Among ten candidates, peptide P05 (ADDGRPFPQVIK), a fragment of aldolase A (ALDOA), presented the most potent OS-suppressing capabilities. Its efficacy was additive with standard-of-care chemotherapeutic agents such as cisplatin and doxorubicin, and it downregulated oncoproteins such as epidermal growth factor receptor (EGFR), Snail, and Src in OS cells. Interestingly, P05 did not present inhibitory effects on non-OS skeletal cells such as mesenchymal stem cells and osteoblast cells. Collectively, this study demonstrated that iTSC-derived secretomes may provide a source for identifying anticancer peptides, and P05 may warrant further evaluations for the treatment of OS.
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    Effects of Alpha-Connexin Carboxyl-Terminal Peptide (aCT1) and Bowman-Birk Protease Inhibitor (BBI) on Canine Oral Mucosal Melanoma (OMM) Cells
    (Frontiers Media, 2021-06-10) Sato, Ayami; da Fonseca, Ivone Izabel Mackowiak; Nagamine, Márcia Kazumi; de Toledo, Gabriela Fernandes; Olio, Rennan; Hernandez-Blazquez, Francisco Javier; Yano, Tomohiro; Yeh, Elizabeth Shinmay; Dagli, Maria Lucia Zaidan; Pharmacology and Toxicology, School of Medicine
    Oral mucosal melanomas (OMM) are aggressive cancers in dogs, and are good models for human OMM. Gap junctions are composed of connexin units, which may have altered expression patterns and/or subcellular localization in cancer cells. Cell-to-cell communication by gap junctions is often impaired in cancer cells, including in melanomas. Meanwhile, the upregulated expression of the gap junction protein connexin 43 (Cx43) inhibits melanoma progression. The α-connexin carboxyl-terminal (aCT1) peptide reportedly maintains Cx43 expression and cell-cell communication in human mammary cells and increases the communication activity through gap junctions in functional assays, therefore causing decreased cell proliferation. The Bowman-Birk protease inhibitor (BBI), a component of soybeans, induces Cx43 expression in several tumor cells as a trypsin–chymotrypsin inhibition function, with antineoplastic effects. This study investigated the effect of aCT1 peptide and BBI treatment, alone or in combination, on TLM1 canine melanoma cell viability. Cell viability after treatment with aCT1, the reverse sequence peptide (R-pep), and/or BBI for 5 days was analyzed by PrestoBlue assay. Immunofluorescence was used to observe Cx43 localization and expression. aCT1 (200 μM) alone did not significantly decrease cell viability in TLM1 cells, whereas BBI (400 μg/ml) alone significantly decreased the TLM1 viability. Combined treatment with both aCT1 (200 μM) and BBI (400 μg/ml) significantly decreased cell viability in TLM1 cells. Cx43 expression, as identified by immunostainings in TLM1 cells, was increased in the cell membrane after the combination treatment with BBI and aCT1. This dual treatment can be combined to achieve the anticancer activity, possibly by increasing Cx 43 expression and affecting Cx43 migration to the cell membrane. In conclusion, a treatment strategy targeting Cx43 with BBI and aCT1 may possibly lead to new effective therapies for canine OMM.
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    Pathways of Antigen Processing
    (Annual Reviews, 2013) Blum, Janice S.; Wearsch, Pamela A.; Cresswell, Peter; Microbiology and Immunology, School of Medicine
    T cell recognition of antigen-presenting cells depends on their expression of a spectrum of peptides bound to major histocompatibility complex class I (MHC-I) and class II (MHC-II) molecules. Conversion of antigens from pathogens or transformed cells into MHC-I- and MHC-II-bound peptides is critical for mounting protective T cell responses, and similar processing of self proteins is necessary to establish and maintain tolerance. Cells use a variety of mechanisms to acquire protein antigens, from translation in the cytosol to variations on the theme of endocytosis, and to degrade them once acquired. In this review, we highlight the aspects of MHC-I and MHC-II biosynthesis and assembly that have evolved to intersect these pathways and sample the peptides that are produced.
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