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Antibodies against Clonorchis sinensis LDH could cross-react with LDHB localizing on the plasma membrane of human hepatocarcinoma cell SMMC-7721 and induce apoptosis

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Abstract

Lactate dehydrogenase (LDH) is a terminal enzyme in anaerobic glycolytic pathway. It widely exists in various organisms and is in charge of converting the glycolysis product pyruvic acid to lactic acid. Most parasites, including Clonorchis sinensis, predominantly depend on glycolysis to provide energy. Bioinformatic analysis predicts that the LDHs from many species have more than one transmembrane region, suggesting that it may be a membrane protein. C. sinensis LDH (CsLDH) has been confirmed as a transmembrane protein mainly located in the tegument. The antibodies against CsLDH can inhibit the worm’s energy metabolism, kill the worm, and may have the same effects on human cancer cells. In this study, we cloned and characterized human LDHA (HsLDHA), HsLDHB, and CsLDH. Semi-quantitative real-time RCP showed that HsLDHB only existed in hepatocarcinoma cell SMMC-7721. Confocal microscopy and Western blot experiments revealed that HsLDHB was localized in the plasma membrane of SMMC-7721 cells, and the antibodies against CsLDH could cross-react with it. This cross-reaction could inhibit the enzymatic activity of HsLDHB. The cancer cells co-cultured with anti-CsLDH sera showed a significant decrease in cell proliferation rate and increases in caspase 9 and reactive oxygen species (ROS) levels. Therefore, anti-CsLDH antibodies can induce the apoptosis of cancer cells SMMC-7721 and may serve as a new tool to inhibit tumor.

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    Authors and Affiliations

    1. Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China

      Tianzhang Song, Hongling Yin & Xuchu Hu

    2. Education Ministry Key Laboratory for Tropical Disease Control Research, Sun Yat-sen University, Guangzhou, Guangdong, China

      Tianzhang Song, Hongling Yin & Xuchu Hu

    3. Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

      Wenjia Gan

    4. Department of Clinical Laboratory Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangdong, China

      Jintao Chen

    5. Department of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

      Lilin Huang, Tailong He & Huaiqiu Huang

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    1. Tianzhang Song
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    2. Wenjia Gan
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    Correspondence to Huaiqiu Huang or Xuchu Hu.

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    Tianzhang Song and Wenjia Gan contributed equally to this work.

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    Song, T., Gan, W., Chen, J. et al. Antibodies against Clonorchis sinensis LDH could cross-react with LDHB localizing on the plasma membrane of human hepatocarcinoma cell SMMC-7721 and induce apoptosis. Parasitol Res 115, 1595–1603 (2016). https://doi.org/10.1007/s00436-015-4895-z

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    • DOI: https://doi.org/10.1007/s00436-015-4895-z

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