Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Nuciferine Inhibits Skin Cutaneous Melanoma Cell Growth by Suppressing TLR4/NF-κB Signaling

Author(s): Jingxing Xu, Anxin Ying and Tongxin Shi*

Volume 20, Issue 17, 2020

Page: [2099 - 2105] Pages: 7

DOI: 10.2174/1871520620666200811114607

Price: $65

Abstract

Background: Melanoma causes more than 80% of deaths from all dermatologic cancers. Hence, screening and identifying effective compounds to inhibit the growth of melanoma have crucial importance in basic and clinical treatment.

Methods: High throughput screening was performed to screen and identify compounds that have anti-melanoma ability. Melanoma cell and mouse allograft models were used to examine the anti-tumor effects of Nuciferine (NCFR). Western blot, qPCR, and lentivirus overexpression were applied to detect the activation of the TLR4/NF-κB signaling pathway.

Results: NCFR administration significantly suppressed melanoma cell growth and tumor size by inhibiting the phosphorylation of p65. NCFR treatment also could suppress TNF-α-induced activation of NF-κB signaling. The anti-tumor effect of NCFR might be mediated by targeting Toll-like receptors 4.

Conclusion: NCFR inhibits melanoma cell growth and suppresses tumor size, which provides potential therapeutic strategies for melanoma treatment.

Keywords: Nuciferine, NF-κB, TLR4, p65, melanoma, qPCR.

« Previous Next »
Graphical Abstract

[1]
Miller, A.J.; Mihm, M.C., Jr Melanoma. N. Engl. J. Med., 2006, 355(1), 51-65.
[http://dx.doi.org/10.1056/NEJMra052166] [PMID: 16822996]
[2]
Schadendorf, D.; van Akkooi, A.C.J.; Berking, C.; Griewank, K.G.; Gutzmer, R.; Hauschild, A.; Stang, A.; Roesch, A.; Ugurel, S. Melanoma. Lancet, 2018, 392(10151), 971-984.
[http://dx.doi.org/10.1016/S0140-6736(18)31559-9] [PMID: 30238891]
[3]
Zbytek, B.; Carlson, J.A.; Granese, J.; Ross, J.; Mihm, M.C., Jr; Slominski, A. Current concepts of metastasis in melanoma. Expert. Rev. Dermatol., 2008, 3(5), 569-585.
[http://dx.doi.org/10.1586/17469872.3.5.569] [PMID: 19649148]
[4]
Bhuchar, S.; Katta, R.; Wolf, J. Complementary and alternative medicine in dermatology: An overview of selected modalities for the practicing dermatologist. Am. J. Clin. Dermatol., 2012, 13(5), 311-317.
[http://dx.doi.org/10.2165/11597560-000000000-00000] [PMID: 22668453]
[5]
Kwon, H.J.; Choi, G.E.; Ryu, S.; Kwon, S.J.; Kim, S.C.; Booth, C.; Nichols, K.E.; Kim, H.S. Stepwise phosphorylation of p65 promotes NF-κB activation and NK cell responses during target cell recognition. Nat. Commun., 2016, 7, 11686.
[http://dx.doi.org/10.1038/ncomms11686] [PMID: 27221592]
[6]
Thapa, R.J.; Nogusa, S.; Chen, P.; Maki, J.L.; Lerro, A.; Andrake, M.; Rall, G.F.; Degterev, A.; Balachandran, S. Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases. Proc. Natl. Acad. Sci. USA, 2013, 110(33), E3109-E3118.
[http://dx.doi.org/10.1073/pnas.1301218110] [PMID: 23898178]
[7]
Xia, L.; Tan, S.; Zhou, Y.; Lin, J.; Wang, H.; Oyang, L.; Tian, Y.; Liu, L.; Su, M.; Wang, H.; Cao, D.; Liao, Q. Role of the NFκB-signaling pathway in cancer. OncoTargets Ther., 2018, 11, 2063-2073.
[http://dx.doi.org/10.2147/OTT.S161109] [PMID: 29695914]
[8]
Taniguchi, K.; Karin, M. NF-κB, inflammation, immunity and cancer: Coming of age. Nat. Rev. Immunol., 2018, 18(5), 309-324.
[http://dx.doi.org/10.1038/nri.2017.142] [PMID: 29379212]
[9]
Andjelic, S.; Hsia, C.; Suzuki, H.; Kadowaki, T.; Koyasu, S.; Liou, H.C. Phosphatidylinositol 3-kinase and NF-kappa B/Rel are at the divergence of CD40-mediated proliferation and survival pathways. J. Immunol., 2000, 165(7), 3860-3867.
[http://dx.doi.org/10.4049/jimmunol.165.7.3860] [PMID: 11034392]
[10]
Ehrhardt, H.; Fulda, S.; Schmid, I.; Hiscott, J.; Debatin, K.M.; Jeremias, I. TRAIL induced survival and proliferation in cancer cells resistant towards TRAIL-induced apoptosis mediated by NF-kappaB. Oncogene, 2003, 22(25), 3842-3852.
[http://dx.doi.org/10.1038/sj.onc.1206520] [PMID: 12813457]
[11]
Pratt, M.A.; Tibbo, E.; Robertson, S.J.; Jansson, D.; Hurst, K.; Perez-Iratxeta, C.; Lau, R.; Niu, M.Y. The canonical NF-kappaB pathway is required for formation of luminal mammary neoplasias and is activated in the mammary progenitor population. Oncogene, 2009, 28(30), 2710-2722.
[http://dx.doi.org/10.1038/onc.2009.131] [PMID: 19483731]
[12]
Guttridge, D.C.; Albanese, C.; Reuther, J.Y.; Pestell, R.G.; Baldwin, A.S., Jr NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol. Cell. Biol., 1999, 19(8), 5785-5799.
[http://dx.doi.org/10.1128/MCB.19.8.5785] [PMID: 10409765]
[13]
Wang, C.Y.; Guttridge, D.C.; Mayo, M.W.; Baldwin, A.S., Jr NF-kappaB induces expression of the Bcl-2 homologue A1/Bfl-1 to preferentially suppress chemotherapy-induced apoptosis. Mol. Cell. Biol., 1999, 19(9), 5923-5929.
[http://dx.doi.org/10.1128/MCB.19.9.5923] [PMID: 10454539]
[14]
Sakurai, H.; Chiba, H.; Miyoshi, H.; Sugita, T.; Toriumi, W. IkappaB kinases phosphorylate NF-kappaB p65 subunit on serine 536 in the transactivation domain. J. Biol. Chem., 1999, 274(43), 30353-30356.
[http://dx.doi.org/10.1074/jbc.274.43.30353] [PMID: 10521409]
[15]
Karin, M.; Delhase, M. The I kappa B kinase (IKK) and NF-kappa B: Key elements of proinflammatory signalling. Semin. Immunol., 2000, 12(1), 85-98.
[http://dx.doi.org/10.1006/smim.2000.0210] [PMID: 10723801]
[16]
Küper, C.; Beck, F.X.; Neuhofer, W. Toll-like receptor 4 activates NF-κB and MAP kinase pathways to regulate expression of proinflammatory COX-2 in renal medullary collecting duct cells. Am. J. Physiol. Renal Physiol., 2012, 302(1), F38-F46.
[http://dx.doi.org/10.1152/ajprenal.00590.2010] [PMID: 21937604]
[17]
Ho, H.H.; Hsu, L.S.; Chan, K.C.; Chen, H.M.; Wu, C.H.; Wang, C.J. Extract from the leaf of nucifera reduced the development of atherosclerosis via inhibition of vascular smooth muscle cell proliferation and migration. Food Chem. Toxicol., 2010, 48(1), 159-168.
[http://dx.doi.org/10.1016/j.fct.2009.09.033] [PMID: 19799955]
[18]
Guo, F.; Yang, X.; Li, X.; Feng, R.; Guan, C.; Wang, Y.; Li, Y.; Sun, C. Nuciferine prevents hepatic steatosis and injury induced by a high-fat diet in hamsters. PLoS One, 2013, 8(5)e63770
[http://dx.doi.org/10.1371/journal.pone.0063770] [PMID: 23691094]
[19]
Lu, Y.L.; He, Y.Q.; Wang, M.; Zhang, L.; Yang, L.; Wang, Z.T.; Ji, G. Characterization of nuciferine metabolism by P450 enzymes and uridine diphosphate glucuronosyltransferases in liver microsomes from humans and animals. Acta Pharmacol. Sin., 2010, 31(12), 1635-1642.
[http://dx.doi.org/10.1038/aps.2010.172] [PMID: 21127497]
[20]
Nguyen, K.H.; Ta, T.N.; Pham, T.H.; Nguyen, Q.T.; Pham, H.D.; Mishra, S.; Nyomba, B.L. Nuciferine stimulates insulin secretion from beta cells-an in vitro comparison with glibenclamide. J. Ethnopharmacol., 2012, 142(2), 488-495.
[http://dx.doi.org/10.1016/j.jep.2012.05.024] [PMID: 22633982]
[21]
Wang, M.X.; Liu, Y.L.; Yang, Y.; Zhang, D.M.; Kong, L.D. Nuciferine restores potassium oxonate-induced hyperuricemia and kidney inflammation in mice. Eur. J. Pharmacol., 2015, 747, 59-70.
[http://dx.doi.org/10.1016/j.ejphar.2014.11.035] [PMID: 25499818]
[22]
Yuan, S.M.; Li, H.; Yang, M.; Zha, H.; Sun, H.; Li, X.R.; Li, A.F.; Gu, Y.; Duan, L.; Luo, J.Y.; Li, C.Y.; Wang, Y.; Wang, Z.B.; He, T.C.; Zhou, L. High intensity focused ultrasound enhances anti-tumor immunity by inhibiting the negative regulatory effect of miR-134 on CD86 in a murine melanoma model. Oncotarget, 2015, 6(35), 37626-37637.
[http://dx.doi.org/10.18632/oncotarget.5285] [PMID: 26485753]
[23]
Zhang, W.; Shao, W.; Dong, Z.; Zhang, S.; Liu, C.; Chen, S. Cloxiquine, a traditional antituberculosis agent, suppresses the growth and metastasis of melanoma cells through activation of PPARγ. Cell Death Dis., 2019, 10(6), 404.
[http://dx.doi.org/10.1038/s41419-019-1644-8] [PMID: 31138783]
[24]
Dadras, S.S.; Paul, T.; Bertoncini, J.; Brown, L.F.; Muzikansky, A.; Jackson, D.G.; Ellwanger, U.; Garbe, C.; Mihm, M.C.; Detmar, M. Tumor lymphangiogenesis: A novel prognostic indicator for cutaneous melanoma metastasis and survival. Am. J. Pathol., 2003, 162(6), 1951-1960.
[http://dx.doi.org/10.1016/S0002-9440(10)64328-3] [PMID: 12759251]
[25]
Payne, A.S.; Cornelius, L.A. The role of chemokines in melanoma tumor growth and metastasis. J. Invest. Dermatol., 2002, 118(6), 915-922.
[http://dx.doi.org/10.1046/j.1523-1747.2002.01725.x] [PMID: 12060384]
[26]
Ueda, Y.; Richmond, A. NF-kappaB activation in melanoma. Pigment Cell Res., 2006, 19(2), 112-124.
[http://dx.doi.org/10.1111/j.1600-0749.2006.00304.x] [PMID: 16524427]
[27]
Xu, X.; Wang, J.; Han, K.; Li, S.; Xu, F.; Yang, Y. Antimalarial drug mefloquine inhibits nuclear factor kappa B signaling and induces apoptosis in colorectal cancer cells. Cancer Sci., 2018, 109(4), 1220-1229.
[http://dx.doi.org/10.1111/cas.13540] [PMID: 29453896]
[28]
Patel, P.S.; Varney, M.L.; Dave, B.J.; Singh, R.K. Regulation of constitutive and induced NF-kappaB activation in malignant melanoma cells by capsaicin modulates interleukin-8 production and cell proliferation. J. Interferon Cytokine Res., 2002, 22(4), 427-435.
[http://dx.doi.org/10.1089/10799900252952217] [PMID: 12034025]
[29]
Wang, M.X.; Zhao, X.J.; Chen, T.Y.; Liu, Y.L.; Jiao, R.Q.; Zhang, J.H.; Ma, C.H.; Liu, J.H.; Pan, Y.; Kong, L.D. Nuciferine alleviates renal injury by inhibiting inflammatory responses in fructose-fed rats. J. Agric. Food Chem., 2016, 64(42), 7899-7910.
[http://dx.doi.org/10.1021/acs.jafc.6b03031] [PMID: 27718563]
[30]
Zhang, D.D.; Zhang, J.G.; Wu, X.; Liu, Y.; Gu, S.Y.; Zhu, G.H.; Wang, Y.Z.; Liu, G.L.; Li, X.Y. Nuciferine downregulates Per-Arnt-Sim kinase expression during its alleviation of lipogenesis and inflammation on oleic acid-induced hepatic steatosis in HepG2 cells. Front. Pharmacol., 2015, 6, 238.
[http://dx.doi.org/10.3389/fphar.2015.00238] [PMID: 26539118]

Rights & Permissions Print Cite
Article Metrics
37
© 2024 Bentham Science Publishers | Privacy Policy