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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Research Article

Resveratrol Inhibits Hepatocellular Carcinoma Progression through Regulating Exosome Secretion

Author(s): Kun Tong, Pingfeng Wang, Ying Li, Yaoyao Tong, Xuejie li, Shirong Yan* and Pei Hu*

Volume 31, Issue 15, 2024

Published on: 21 September, 2023

Page: [2107 - 2118] Pages: 12

DOI: 10.2174/0929867331666230914090053

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Abstract

Background and Objectives: Resveratrol is a promising drug for tumor therapy, but its anti-tumor mechanism remains unclarified. The present study aimed to explore the effect of resveratrol on the secretion of exosomes and the role of resveratrol-induced exosomes in the progression of hepatocellular carcinoma.

Methods: The number and contents of exosomes induced by resveratrol were determined by nanoparticle tracking analysis and high-throughput sequencing in Huh7 cells, respectively. Expression of Rab27a was assessed by Western blotting and immunofluorescence. Cell proliferation, migration and epithelial-mesenchymal transition were examined with the stimuli of resveratrol and exosomes, the activity of autophagy and wnt/β-catenin signaling induced by resveratrol-induced exosomes and knockdown of lncRNA SNHG29 were monitored by Western blotting and immunofluorescence.

Results: It was found that resveratrol might inhibit the exosome secretion by down-regulating the expression of Rab27a, thereby suppressing the proliferation, migration and epithelial-mesenchymal transition of Huh7 cells. Moreover, resveratrol-induced exosomes could also inhibit the malignant phenotype of Huh7 cells via inhibiting the nuclear translocation of β-catenin and the activation of autophagy, which lncRNA SNHG29 might mediate.

Conclusion: Resveratrol inhibits hepatocellular carcinoma progression by regulating exosome secretion and contents.

Keywords: Hepatocellular carcinoma, resveratrol, exosome, autophagy, lncRNA, nano-particle.

« Previous Next »
[1]
El-Serag, H.B. Hepatocellular carcinoma. N. Engl. J. Med., 2011, 365(12), 1118-1127.
[http://dx.doi.org/10.1056/NEJMra1001683] [PMID: 21992124]
[2]
Tarantino, G.; Balsano, C.; Santini, S.J.; Brienza, G.; Clemente, I.; Cosimini, B.; Sinatti, G. It is high time physicians thought of natural products for alleviating NAFLD. Is there sufficient evidence to use them? Int. J. Mol. Sci., 2021, 22(24), 13424.
[http://dx.doi.org/10.3390/ijms222413424] [PMID: 34948230]
[3]
Amiri, A.; Mahjoubin-Tehran, M.; Asemi, Z.; Shafiee, A.; Hajighadimi, S.; Moradizarmehri, S.; Mirzaei, H.R.; Mirzaei, H. Role of resveratrol in modulating micrornas in human diseases: From cancer to inflammatory disorder. Curr. Med. Chem., 2021, 28(2), 360-376.
[http://dx.doi.org/10.2174/1875533XMTAyiOTQi2] [PMID: 31830882]
[4]
Almatroodi, S.A.; A Alsahli, M.; S M Aljohani, A.; Alhumaydhi, F.A.; Babiker, A.Y.; Khan, A.A.; Rahmani, A.H. Potential therapeutic targets of resveratrol, a plant polyphenol, and its role in the therapy of various types of cancer. Molecules, 2022, 27(9), 2665.
[http://dx.doi.org/10.3390/molecules27092665] [PMID: 35566016]
[5]
Yang, R.; Dong, H.; Jia, S.; Yang, Z Resveratrol as a modulatory of apoptosis and autophagy in cancer therapy. Clin Transl Oncol, 2022, 24(7), 1219-1230.
[6]
Zhang, L.; Yu, D. Exosomes in cancer development, metastasis, and immunity. Biochim. Biophys. Acta Rev. Cancer, 2019, 1871(2), 455-468.
[http://dx.doi.org/10.1016/j.bbcan.2019.04.004] [PMID: 31047959]
[7]
Ostrowski, M.; Carmo, N.B.; Krumeich, S.; Fanget, I.; Raposo, G.; Savina, A.; Moita, C.F.; Schauer, K.; Hume, A.N.; Freitas, R.P. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol, 2010, 12(1), 19-30.
[http://dx.doi.org/10.1038/ncb2000]
[8]
Zhou, W.; Zheng, X.; Cheng, C.; Guo, G.; Zhong, Y.; Liu, W.; Liu, K.; Chen, Y.; Liu, S.; Liu, S. Rab27a deletion impairs the therapeutic potential of endothelial progenitor cells for myocardial infarction. Mol. Cell. Biochem., 2021, 476(2), 797-807.
[http://dx.doi.org/10.1007/s11010-020-03945-x] [PMID: 33095380]
[9]
Guo, K.; Feng, Y.; Zheng, X.; Sun, L.; Wasan, H.S.; Ruan, S.; Shen, M. Resveratrol and its analogs: Potent agents to reverse epithelial-to-mesenchymal transition in tumors. Front. Oncol., 2021, 11, 644134.
[http://dx.doi.org/10.3389/fonc.2021.644134] [PMID: 33937049]
[10]
Pegtel, D.M.; Gould, S.J. Exosomes. Annu. Rev. Biochem., 2019, 88(1), 487-514.
[http://dx.doi.org/10.1146/annurev-biochem-013118-111902] [PMID: 31220978]
[11]
Song, L.; Tang, S.; Han, X.; Jiang, Z.; Dong, L.; Liu, C.; Liang, X.; Dong, J.; Qiu, C.; Wang, Y.; Du, Y. KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a. Nat. Commun., 2019, 10(1), 1639.
[http://dx.doi.org/10.1038/s41467-019-09720-x] [PMID: 30967557]
[12]
Guo, D.; Lui, G.Y.L.; Lai, S.L.; Wilmott, J.S.; Tikoo, S.; Jackett, L.A.; Quek, C.; Brown, D.L.; Sharp, D.M.; Kwan, R.Y.Q.; Chacon, D.; Wong, J.H.; Beck, D.; Geldermalsen, M.; Holst, J.; Thompson, J.F.; Mann, G.J.; Scolyer, R.A.; Stow, J.L.; Weninger, W.; Haass, N.K.; Beaumont, K.A. RAB27A promotes melanoma cell invasion and metastasis via regulation of pro-invasive exosomes. Int. J. Cancer, 2019, 144(12), 3070-3085.
[http://dx.doi.org/10.1002/ijc.32064] [PMID: 30556600]
[13]
Li, X.; Li, C.; Zhang, L.; Wu, M.; Cao, K.; Jiang, F.; Chen, D.; Li, N.; Li, W. The significance of exosomes in the development and treatment of hepatocellular carcinoma. Mol. Cancer, 2020, 19(1), 1.
[http://dx.doi.org/10.1186/s12943-019-1085-0] [PMID: 31901224]
[14]
Xie, Q.H.; Zheng, J.Q.; Ding, J.Y.; Wu, Y.F.; Liu, L.; Yu, Z.L.; Chen, G. Exosome-mediated immunosuppression in tumor microenvironments. Cells, 2022, 11(12), 1946.
[http://dx.doi.org/10.3390/cells11121946] [PMID: 35741075]
[15]
Yang, K.; Zhou, Q.; Qiao, B.; Shao, B.; Hu, S.; Wang, G.; Yuan, W.; Sun, Z. Exosome-derived noncoding RNAs: Function, mechanism, and application in tumor angiogenesis. Mol. Ther. Nucleic Acids, 2022, 27, 983-997.
[http://dx.doi.org/10.1016/j.omtn.2022.01.009] [PMID: 35317280]
[16]
Ge, Y.; Mu, W.; Ba, Q.; Li, J.; Jiang, Y.; Xia, Q.; Wang, H. Hepatocellular carcinoma-derived exosomes in organotropic metastasis, recurrence and early diagnosis application. Cancer Lett., 2020, 477, 41-48.
[http://dx.doi.org/10.1016/j.canlet.2020.02.003] [PMID: 32112905]
[17]
Meng, W.; Hao, Y.; He, C.; Li, L.; Zhu, G. Exosome-orchestrated hypoxic tumor microenvironment. Mol. Cancer, 2019, 18(1), 57.
[http://dx.doi.org/10.1186/s12943-019-0982-6] [PMID: 30925935]
[18]
Richards, K.E.; Zeleniak, A.E.; Fishel, M.L.; Wu, J.; Littlepage, L.E.; Hill, R. Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene, 2017, 36(13), 1770-1778.
[http://dx.doi.org/10.1038/onc.2016.353] [PMID: 27669441]
[19]
Matsumoto, A.; Takahashi, Y.; Nishikawa, M.; Sano, K.; Morishita, M.; Charoenviriyakul, C.; Saji, H.; Takakura, Y. Accelerated growth of B16 BL 6 tumor in mice through efficient uptake of their own exosomes by B16 BL 6 cells. Cancer Sci., 2017, 108(9), 1803-1810.
[http://dx.doi.org/10.1111/cas.13310] [PMID: 28667694]
[20]
Xue, M.; Chen, W.; Xiang, A.; Wang, R.; Chen, H.; Pan, J.; Pang, H.; An, H.; Wang, X.; Hou, H.; Li, X. Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1. Mol. Cancer, 2017, 16(1), 143.
[http://dx.doi.org/10.1186/s12943-017-0714-8] [PMID: 28841829]
[21]
Chen, R.; Xu, X.; Tao, Y.; Qian, Z.; Yu, Y. Exosomes in hepatocellular carcinoma: A new horizon. Cell Commun. Signal., 2019, 17(1), 1.
[http://dx.doi.org/10.1186/s12964-018-0315-1] [PMID: 30616541]
[22]
Yang, L.; Peng, X.; Li, Y.; Zhang, X.; Ma, Y.; Wu, C.; Fan, Q.; Wei, S.; Li, H.; Liu, J. Long non-coding RNA HOTAIR promotes exosome secretion by regulating RAB35 and SNAP23 in hepatocellular carcinoma. Mol. Cancer, 2019, 18(1), 78.
[http://dx.doi.org/10.1186/s12943-019-0990-6] [PMID: 30943982]
[23]
Chen, L.; Guo, P.; He, Y.; Chen, Z.; Chen, L.; Luo, Y.; Qi, L.; Liu, Y.; Wu, Q.; Cui, Y.; Fang, F.; Zhang, X.; Song, T.; Guo, H. HCC-derived exosomes elicit HCC progression and recurrence by epithelial-mesenchymal transition through MAPK/ERK signalling pathway. Cell Death Dis., 2018, 9(5), 513.
[http://dx.doi.org/10.1038/s41419-018-0534-9] [PMID: 29725020]
[24]
Yazdani, H.; Huang, H.; Tsung, A. Autophagy: Dual response in the development of hepatocellular carcinoma. Cells, 2019, 8(2), 91.
[http://dx.doi.org/10.3390/cells8020091] [PMID: 30695997]
[25]
Ma, W.; Zhou, Y.; Liu, M.; Qin, Q.; Cui, Y. Long non-coding RNA LINC00470 in serum derived exosome: A critical regulator for proliferation and autophagy in glioma cells. Cancer Cell Int., 2021, 21(1), 149.
[http://dx.doi.org/10.1186/s12935-021-01825-y] [PMID: 33663509]
[26]
Yao, W.; Guo, P.; Mu, Q.; Wang, Y. Exosome-derived circ-PVT1 contributes to cisplatin resistance by regulating autophagy, invasion, and apoptosis via miR-30a-5p/YAP1 axis in gastric cancer cells. Cancer Biother. Radiopharm., 2021, 36(4), 347-359.
[http://dx.doi.org/10.1089/cbr.2020.3578] [PMID: 32799541]

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