Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Sauchinone Inhibits the Proliferation and Immune Invasion Capacity of Colorectal Cancer Cells through the Suppression of PD-L1 and MMP2/MM9

Author(s): Yiping Lu*, Miao Yu, Jinsheng Ye, Yankai Liang, Jianxin Gao, Zhen Ji and Jie Wang

Volume 23, Issue 12, 2023

Published on: 14 April, 2023

Page: [1406 - 1414] Pages: 9

DOI: 10.2174/1871520623666230320125406

Price: $65

conference banner
Abstract

Background: Colorectal cancer (CRC) is one of the most common tumors globally and a leading cause of cancer-related death. In China, CRC is the third most common cancer type. Sauchinone is known to exhibit anti-tumor and anti-inflammatory activity, but its effects on CRC have not been investigated to-date

Objective: To investigate the effects of Sauchinone on CRC development and metastasis and its underlying mechanism( s) of action.

Methods: SW480 and HCT116 cells were treated with a range of concentrations of Sauchinone. Cell proliferation was measured using EDU assays and flow cytometry.

Results: Treatment with 50 μM Sauchinone decreased the expression of MMP2 and MMP9 and downregulated PD-L1 expression (PD-1/PD-L1) leading to checkpoint inhibition. Sauchinone treatment also enhanced the cytotoxicity of SW840 and HCT116 cells co-cultured with CD8+ T cells. The overexpression of PD-L1 rescued the anti-proliferative and cytotoxic effects of Sauchinone in both types.

Conclusions: We show that Sauchinone suppresses CRC cell growth through the downregulation of MMP2 and MM9 expression and PD-1/PD-L1 mediated checkpoint inhibition. Collectively, these data highlight the promise of Sauchinone as a future anti-CRC therapeutic.

Graphical Abstract

[1]
Xi, Y.; Xu, P. Global colorectal cancer burden in 2020 and projections to 2040. Transl. Oncol., 2021, 14(10), 101174.
[http://dx.doi.org/10.1016/j.tranon.2021.101174] [PMID: 34243011]
[2]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[3]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin., 2020, 70(1), 7-30.
[http://dx.doi.org/10.3322/caac.21590] [PMID: 31912902]
[4]
(a) Jung, Y.W.; Lee, B.M.; Ha, M.T.; Tran, M.H.; Kim, J.A.; Lee, S.; Lee, J.H.; Woo, M.H.; Min, B.S. Lignans from Saururus chinensis exhibit anti-inflammatory activity by influencing the Nrf2/HO-1 activation pathway. Arch. Pharm. Res., 2019, 42(4), 332-343.
[http://dx.doi.org/10.1007/s12272-018-1093-4] [PMID: 30610615];
(b) Cheng, Y.; Yin, Z.; Jiang, F.; Xu, J.; Chen, H.; Gu, Q. Two new lignads from the aerial parts of Saururus chinensis with cytotoxicity toward nasopharyngeal carcinoma. Fitoterapia, 2020, 141, 104344.
[http://dx.doi.org/10.1016/j.fitote.2019.104344] [PMID: 31465814];
(c) Kim, N.H.; Sung, N.J.; Shin, S.; Ryu, D.S.; Youn, H.S.; Park, S.A. Sauchinone inhibits the proliferation, migration and invasion of breast cancer cells by suppressing Akt-CREB-MMP13 signaling pathway. Biosci. Rep., 2021, 41(10), BSR20211067.
[http://dx.doi.org/10.1042/BSR20211067] [PMID: 34643237]
[5]
(a) Cui, H.; Xu, B.; Wu, T.; Xu, J.; Yuan, Y.; Gu, Q. Potential antiviral lignans from the roots of Saururus chinensis with activity against Epstein-Barr virus lytic replication. J. Nat. Prod., 2014, 77(1), 100-110.
[http://dx.doi.org/10.1021/np400757k] [PMID: 24359277];
(b) Park, H.J.; Kim, R.G.; Seo, B.R.; Ha, J.; Ahn, B.T.; Bok, S.H.; Lee, Y.S.; Kim, H.J.; Lee, K.T. Saucernetin-7 and saucernetin-8 isolated from Saururus chinensis inhibit the LPS-induced production of nitric oxide and prostaglandin E2 in macrophage RAW264.7 cells. Planta Med., 2003, 69(10), 947-950.
[http://dx.doi.org/10.1055/s-2003-45106] [PMID: 14648400];
(c) Ryu, S.Y.; Oh, K.S.; Kim, Y.S.; Lee, B.H. Antihypertensive, vasorelaxant and inotropic effects of an ethanolic extract of the roots of Saururus chinensis. J. Ethnopharmacol., 2008, 118(2), 284-289.
[http://dx.doi.org/10.1016/j.jep.2008.04.011] [PMID: 18495395];
(d) Lee, Y.J.; Kim, J.; Yi, J.M.; Oh, S.M.; Kim, N.S.; Kim, H.; Oh, D.S.; Bang, O.S.; Lee, J. Anti-proliferative neolignans from Saururus chinensis against human cancer cell lines. Biol. Pharm. Bull., 2012, 35(8), 1361-1366.
[http://dx.doi.org/10.1248/bpb.b110670] [PMID: 22863938];
(e) Seo, C.S.; Lee, Y.K.; Kim, Y.J.; Jung, J.S.; Jahng, Y.; Chang, H.W.; Song, D.K.; Son, J.K. Protective effect of lignans against sepsis from the roots of Saururus chinensis. Biol. Pharm. Bull., 2008, 31(3), 523-526.
[http://dx.doi.org/10.1248/bpb.31.523] [PMID: 18310923]
[6]
Kim, Y.W.; Jang, E.J.; Kim, C.H.; Lee, J.H. Sauchinone exerts anticancer effects by targeting AMPK signaling in hepatocellular carcinoma cells. Chem. Biol. Interact., 2017, 261, 108-117.
[http://dx.doi.org/10.1016/j.cbi.2016.11.016] [PMID: 27871897]
[7]
Li, S.Q.; Feng, J.; Yang, M.; Ai, X.P.; He, M.; Liu, F. Sauchinone: A prospective therapeutic agent-mediated EIF4EBP1 down-regulation suppresses proliferation, invasion and migration of lung adenocarcinoma cells. J. Nat. Med., 2020, 74(4), 777-787.
[http://dx.doi.org/10.1007/s11418-020-01435-4] [PMID: 32666278]
[8]
Fu, S.H.; Chien, M.W.; Hsu, C.Y.; Liu, Y.W.; Sytwu, H.K. Interplay between cytokine circuitry and transcriptional regulation shaping helper T Cell pathogenicity and plasticity in inflammatory bowel disease. Int. J. Mol. Sci., 2020, 21(9), 3379.
[http://dx.doi.org/10.3390/ijms21093379] [PMID: 32403220]
[9]
Cabral-Pacheco, G.A.; Garza-Veloz, I.; Castruita-De la Rosa, C.; Ramirez-Acuña, J.M.; Perez-Romero, B.A.; Guerrero-Rodriguez, J.F.; Martinez-Avila, N.; Martinez-Fierro, M.L. The roles of matrix metalloproteinases and their inhibitors in human diseases. Int. J. Mol. Sci., 2020, 21(24), 9739.
[http://dx.doi.org/10.3390/ijms21249739] [PMID: 33419373]
[10]
Visse, R.; Nagase, H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry. Circ. Res., 2003, 92(8), 827-839.
[http://dx.doi.org/10.1161/01.RES.0000070112.80711.3D] [PMID: 12730128]
[11]
(a) Almalki, S.G.; Agrawal, D.K. Effects of matrix metalloproteinases on the fate of mesenchymal stem cells. Stem Cell Res. Ther., 2016, 7(1), 129.
[http://dx.doi.org/10.1186/s13287-016-0393-1] [PMID: 27612636];
(b) Singer, C.F.; Kronsteiner, N.; Marton, E.; Kubista, M.; Cullen, K.J.; Hirtenlehner, K.; Seifert, M.; Kubista, E. MMP-2 and MMP-9 expression in breast cancer-derived human fibroblasts is differentially regulated by stromal-epithelial interactions. Breast Cancer Res. Treat., 2002, 72(1), 69-77.
[http://dx.doi.org/10.1023/A:1014918512569] [PMID: 12000221]
[12]
(a) Huang, H. Matrix Metalloproteinase-9 (MMP-9) as a cancer biomarker and MMP-9 biosensors: Recent advances. Sensors, 2018, 18(10), 3249.
[http://dx.doi.org/10.3390/s18103249] [PMID: 30262739];
(b) Hicklin, D.J.; Ellis, L.M. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol., 2005, 23(5), 1011-1027.
[http://dx.doi.org/10.1200/JCO.2005.06.081] [PMID: 15585754];
(c) Han, I.; Lee, M.R.; Nam, K.W.; Oh, J.H.; Moon, K.C.; Kim, H.S. Expression of macrophage migration inhibitory factor relates to survival in high-grade osteosarcoma. Clin. Orthop. Relat. Res., 2008, 466(9), 2107-2113.
[http://dx.doi.org/10.1007/s11999-008-0333-1] [PMID: 18563508];
(d) Loukopoulos, P.; Mungall, B.A.; Straw, R.C.; Thornton, J.R.; Robinson, W.F. Matrix metalloproteinase-2 and -9 involvement in canine tumors. Vet. Pathol., 2003, 40(4), 382-394.
[http://dx.doi.org/10.1354/vp.40-4-382] [PMID: 12824510];
(e) Chen, Q.; Jin, M.; Yang, F.; Zhu, J.; Xiao, Q.; Zhang, L. Matrix metalloproteinases: Inflammatory regulators of cell behaviors in vascular formation and remodeling. Mediators Inflamm., 2013, 2013, 928315.
[http://dx.doi.org/10.1155/2013/928315] [PMID: 23840100]
[13]
(a) Blank, C.; Gajewski, T.F.; Mackensen, A. Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: Implications for tumor immunotherapy. Cancer Immunol. Immunother., 2005, 54(4), 307-314.
[http://dx.doi.org/10.1007/s00262-004-0593-x] [PMID: 15599732];
(b) Iwai, Y.; Ishida, M.; Tanaka, Y.; Okazaki, T.; Honjo, T.; Minato, N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl. Acad. Sci. USA, 2002, 99(19), 12293-12297.
[http://dx.doi.org/10.1073/pnas.192461099] [PMID: 12218188];
(c) Husain, N.; Srivastava, P.; Shukla, S.; Chauhan, S.; Pandey, A.; Masood, S. PD-L1 Expression in colorectal carcinoma and its correlation with clinicopathological parameters, microsatellite instability and BRAF mutation. Indian J. Pathol. Microbiol., 2021, 64(3), 490-496.
[http://dx.doi.org/10.4103/IJPM.IJPM_521_20] [PMID: 34341259]
[14]
(a) Reiss, K.A.; Forde, P.M.; Brahmer, J.R. Harnessing the power of the immune system via blockade of PD-1 and PD-L1: A promising new anticancer strategy. Immunotherapy, 2014, 6(4), 459-475.
[http://dx.doi.org/10.2217/imt.14.9] [PMID: 24815784];
(b) Lipson, E.J.; Forde, P.M.; Hammers, H.J.; Emens, L.A.; Taube, J.M.; Topalian, S.L. Antagonists of PD-1 and PD-L1 in cancer treatment. Semin. Oncol., 2015, 42(4), 587-600.
[http://dx.doi.org/10.1053/j.seminoncol.2015.05.013] [PMID: 26320063]
[15]
Yokosuka, T.; Takamatsu, M.; Kobayashi-Imanishi, W.; Hashimoto-Tane, A.; Azuma, M.; Saito, T. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J. Exp. Med., 2012, 209(6), 1201-1217.
[http://dx.doi.org/10.1084/jem.20112741] [PMID: 22641383]
[16]
(a) Liu, J.; Hamrouni, A.; Wolowiec, D.; Coiteux, V.; Kuliczkowski, K.; Hetuin, D.; Saudemont, A.; Quesnel, B. Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-γ and TLR ligands via a MyD88, TRAF6, and MEK-dependent pathway. Blood, 2007, 110(1), 296-304.
[http://dx.doi.org/10.1182/blood-2006-10-051482] [PMID: 17363736];
(b) Qian, Y.; Deng, J.; Geng, L.; Xie, H.; Jiang, G.; Zhou, L.; Wang, Y.; Yin, S.; Feng, X.; Liu, J.; Ye, Z.; Zheng, S. TLR4 signaling induces B7-H1 expression through MAPK pathways in bladder cancer cells. Cancer Invest., 2008, 26(8), 816-821.
[http://dx.doi.org/10.1080/07357900801941852] [PMID: 18608206]
[17]
Gong, Q.Z.; Xiao, D.; Feng, F.; Wen, X.D.; Qu, W. ent-Sauchinone as potential anticancer agent inhibiting migration and invasion of human liver cancer cells via suppressing the STAT3 signaling pathway. Chem. Biodivers., 2018, 15(4), e1800024.
[http://dx.doi.org/10.1002/cbdv.201800024] [PMID: 29495104]
[18]
Min, H.J.; Won, H.Y.; Kim, Y.C.; Sung, S.H.; Byun, M.R.; Hwang, J.H.; Hong, J.H.; Hwang, E.S. Suppression of Th2-driven, allergen-induced airway inflammation by sauchinone. Biochem. Biophys. Res. Commun., 2009, 385(2), 204-209.
[http://dx.doi.org/10.1016/j.bbrc.2009.05.039] [PMID: 19450563]
[19]
Kim, H.Y.; Choi, T.W.; Kim, H.J.; Kim, S.M.; Park, K.R.; Jang, H.J.; Lee, E.H.; Kim, C.Y.; Jung, S.H.; Shim, B.S.; Ahn, K.S. A methylene chloride fraction of Saururus chinensis induces apoptosis through the activation of caspase-3 in prostate and breast cancer cells. Phytomedicine, 2011, 18(7), 567-574.
[http://dx.doi.org/10.1016/j.phymed.2010.10.013] [PMID: 21111586]
[20]
Son, H.J.; Moon, A. Epithelial-mesenchymal transition and cell invasion. Toxicol. Res., 2010, 26(4), 245-252.
[http://dx.doi.org/10.5487/TR.2010.26.4.245] [PMID: 24278531]
[21]
Webb, A.H.; Gao, B.T.; Goldsmith, Z.K.; Irvine, A.S.; Saleh, N.; Lee, R.P.; Lendermon, J.B.; Bheemreddy, R.; Zhang, Q.; Brennan, R.C.; Johnson, D.; Steinle, J.J.; Wilson, M.W.; Morales-Tirado, V.M. Inhibition of MMP-2 and MMP-9 decreases cellular migration, and angiogenesis in in vitro models of retinoblastoma. BMC Cancer, 2017, 17(1), 434.
[http://dx.doi.org/10.1186/s12885-017-3418-y] [PMID: 28633655]
[22]
Radisky, E.S.; Radisky, D.C. Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer. J. Mammary Gland Biol. Neoplas., 2010, 15(2), 201-212.
[http://dx.doi.org/10.1007/s10911-010-9177-x] [PMID: 20440544]
[23]
Han, Y.; Liu, D.; Li, L. PD-1/PD-L1 pathway: Current researches in cancer. Am. J. Cancer Res., 2020, 10(3), 727-742.
[PMID: 32266087]
[24]
Ghosh, C.; Luong, G.; Sun, Y. A snapshot of the PD-1/PD-L1 pathway. J. Cancer, 2021, 12(9), 2735-2746.
[http://dx.doi.org/10.7150/jca.57334] [PMID: 33854633]
[25]
Shan, T.; Chen, S.; Wu, T.; Yang, Y.; Li, S.; Chen, X. PD-L1 expression in colon cancer and its relationship with clinical prognosis. Int. J. Clin. Exp. Pathol., 2019, 12(5), 1764-1769.
[PMID: 31933995]
[26]
(a) Maimela, N.R.; Liu, S.; Zhang, Y. Fates of CD8+ T cells in tumor microenvironment. Comput. Struct. Biotechnol. J., 2019, 17, 1-13.
[http://dx.doi.org/10.1016/j.csbj.2018.11.004] [PMID: 30581539];
(b) Nolz, J.C. Molecular mechanisms of CD8+ T cell trafficking and localization. Cell. Mol. Life Sci., 2015, 72(13), 2461-2473.
[http://dx.doi.org/10.1007/s00018-015-1835-0] [PMID: 25577280];
(c) Kim, P.S.; Ahmed, R. Features of responding T cells in cancer and chronic infection. Curr. Opin. Immunol., 2010, 22(2), 223-230.
[http://dx.doi.org/10.1016/j.coi.2010.02.005] [PMID: 20207527]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy