Luteoloside Suppresses Proliferation and Metastasis of Hepatocellular Carcinoma Cells by Inhibition of NLRP3 Inflammasome

作者: Shao-hua Fan , Yan-yan Wang , Jun Lu , Yuan-lin Zheng , Dong-mei Wu

DOI: 10.1371/JOURNAL.PONE.0089961

关键词:

摘要: The inflammasome is a multi-protein complex which when activated regulates caspase-1 activation and IL-1β secretion. Inflammasome mediated by NLR proteins that respond to stimuli. Among NLRs, NLRP3 senses the widest array of plays an important role in development many cancer types. However, Whether process hepatocellular carcinoma (HCC) still unknown. Here, anticancer effect luteoloside, naturally occurring flavonoid isolated from medicinal plant Gentiana macrophylla, against HCC cells underlying mechanisms were investigated. Luteoloside significantly inhibited proliferation vitro vivo. Live-cell imaging transwell assays showed migration invasive capacities cells, treated with compared control cells. inhibitory luteoloside on metastasis was also observed vivo male BALB/c-nu/nu mouse lung model. Further studies could reduce intracellular reactive oxygen species (ROS) accumulation. decreased levels ROS induced accompanied decrease expression resulting proteolytic cleavage caspase-1. Inactivation resulted inhibition IL-1β. Thus, exerts its proliferation, invasion through inflammasome. Our results indicate can be potential therapeutic agent not only as adjuvant therapy for HCC, but also, prevention metastatic HCC.

参考文章(52)
Raul Zamora-Ros, Veronika Fedirko, Antonia Trichopoulou, Carlos A. González, Christina Bamia, Elisabeth Trepo, Ute Nöthlings, Talita Duarte-Salles, Mauro Serafini, Lea Bredsdorff, Kim Overvad, Anne Tjønneland, Jytte Halkjaer, Guy Fagherazzi, Florence Perquier, Marie-Christine Boutron-Ruault, Verena Katzke, Annekatrin Lukanova, Anna Floegel, Heiner Boeing, Pagona Lagiou, Dimitrios Trichopoulos, Calogero Saieva, Claudia Agnoli, Amalia Mattiello, Rosario Tumino, Carlotta Sacerdote, H. Bas Bueno-de-Mesquita, Petra H.M. Peeters, Elisabete Weiderpass, Dagrun Engeset, Guri Skeie, Marcial Vicente Argüelles, Esther Molina-Montes, Miren Dorronsoro, María José Tormo, Eva Ardanaz, Ulrika Ericson, Emily Sonestedt, Malin Sund, Rikard Landberg, Kay-Tee Khaw, Nicholas J. Wareham, Francesca L. Crowe, Elio Riboli, Mazda Jenab, Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study International Journal of Cancer. ,vol. 133, pp. 2429- 2443 ,(2013) , 10.1002/IJC.28257
Yoo Jin Lee, Yu Jin Ha, Yu Na Kang, Koo Jeong Kang, Jae Seok Hwang, Woo Jin Chung, Kwang Bum Cho, Kyung Sik Park, Eun Soo Kim, Hye-Young Seo, Mi-Kyung Kim, Keun-Gyu Park, Byoung Kuk Jang, None, The Autophagy-Related Marker LC3 Can Predict Prognosis in Human Hepatocellular Carcinoma PLOS ONE. ,vol. 8, ,(2013) , 10.1371/JOURNAL.PONE.0081540
Songgang Li, Ping Dong, Jianwei Wang, Jie Zhang, Jun Gu, Xiangsong Wu, Wenguang Wu, Xiaozhou Fei, Zhiping Zhang, Yong Wang, Zhiwei Quan, Yingbin Liu, None, Icariin, a natural flavonol glycoside, induces apoptosis in human hepatoma SMMC-7721 cells via a ROS/JNK-dependent mitochondrial pathway. Cancer Letters. ,vol. 298, pp. 222- 230 ,(2010) , 10.1016/J.CANLET.2010.07.009
Kunlun Chen, Shu Zhang, Yuanyuan Ji, Jun Li, Peng An, Hongtao Ren, Rongrui Liang, Jun Yang, Zongfang Li, Baicalein Inhibits the Invasion and Metastatic Capabilities of Hepatocellular Carcinoma Cells via Down-Regulation of the ERK Pathway PLoS ONE. ,vol. 8, pp. e72927- ,(2013) , 10.1371/JOURNAL.PONE.0072927
Zhi-Jun Dai, Bao-Feng Wang, Wang-Feng Lu, Zhi-Dong Wang, Xiao-Bin Ma, Wei-Li Min, Hua-Feng Kang, Xi-Jing Wang, Wen-Ying Wu, Total flavonoids of Scutellaria barbata inhibit invasion of hepatocarcinoma via MMP/TIMP in vitro. Molecules. ,vol. 18, pp. 934- 950 ,(2013) , 10.3390/MOLECULES18010934
Gina M DeNicola, Florian A Karreth, Timothy J Humpton, Aarthi Gopinathan, Cong Wei, Kristopher Frese, Dipti Mangal, H Yu Kenneth, Charles J Yeo, Eric S Calhoun, Francesca Scrimieri, Jordan M Winter, Ralph H Hruban, Christine Iacobuzio-Donahue, Scott E Kern, Ian A Blair, David A Tuveson, None, Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis Nature. ,vol. 475, pp. 106- 109 ,(2011) , 10.1038/NATURE10189
Mélanie Bruchard, Grégoire Mignot, Valentin Derangère, Fanny Chalmin, Angélique Chevriaux, Frédérique Végran, Wilfrid Boireau, Benoit Simon, Bernhard Ryffel, Jean Louis Connat, Jean Kanellopoulos, François Martin, Cédric Rébé, Lionel Apetoh, François Ghiringhelli, Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth Nature Medicine. ,vol. 19, pp. 57- 64 ,(2013) , 10.1038/NM.2999
Rentian Feng, Shiow Y. Wang, Ying-Hong Shi, Jia Fan, Xiao-Ming Yin, Delphinidin induces necrosis in hepatocellular carcinoma cells in the presence of 3-methyladenine, an autophagy inhibitor Journal of Agricultural and Food Chemistry. ,vol. 58, pp. 3957- 3964 ,(2010) , 10.1021/JF9025458