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The anti-tumor activity of brown seaweed oligo-fucoidan via lncRNA expression modulation in HepG2 cells

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Abstract

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death in Asia. HCC is less sensitive to chemotherapy and is known to express multidrug resistant genes to acquire resistance to chemotherapeutic agents, therefore the development of a potent HCC suppressor is essential in treating HCC. Our previous reports demonstrated that oligo-fucoidan from the brown seaweed Sargassum hemiphyllum elevates microRNA-29b to inhibit epithelial-mesenchymal transition in hepatoma cells. In this study, we aimed to examine in vitro effect of oligo-fucoidan in hepatocellular carcinoma through apoptosis and long noncoding RNA (lncRNA) pathway. Oligo-fucoidan was studied for its anti-hepatoma cells by MTT and DNA ladder analysis. And the mechanism was studied by flow cytometry, qPCR and western blot analysis. In this study, oligo-fucoidan induced sub-G1 phase cell cycle arrest and activation of caspases, indicating that the intrinsic and extrinsic apoptotic pathways were involved in the mechanism of oligo-fucoidan-induced cell death. Moreover, oligo-fucoidan significantly increased the expression of p53, p21, and p27, while cyclin-B1 and -D1 were decreased at the mRNA and protein levels. Finally, we showed that targeting apoptosis and cell cycle pathways could also contribute to the induction of the lncRNA-Saf and lncRNA-p21. Through human lncRNA profiler array analysis, the differential expression of lncRNAs in HCC cells following oligo-fucoidan exposure was further examined. These findings indicated that lncRNAs switched oligo-fucoidan-induced apoptosis, which might be potentially valuable in HCC adjuvant therapy.

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Acknowledgements

Funding was provided by Ministry of Science and Technology, Taiwan (No. 106-2320-B-019-001).

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  1. Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC

    Ming-De Yan

  2. Department of Bioscience and Biotechnology, National Taiwan Ocean University, No. 2, Beining Rd., Jhongjheng District, Keelung City, 202, Taiwan, ROC

    Hsin-Yuan Lin & Pai-An Hwang

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Yan, MD., Lin, HY. & Hwang, PA. The anti-tumor activity of brown seaweed oligo-fucoidan via lncRNA expression modulation in HepG2 cells. Cytotechnology 71, 363–374 (2019). https://doi.org/10.1007/s10616-019-00293-7

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