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30.03.2019 | SHORT REPORT

Discovery and anticancer evaluation of a formononetin derivative against gastric cancer SGC7901 cells

verfasst von: Jian-Ning Yao, Xue-Xiu Zhang, Yan-Zhen Zhang, Jia-Heng Li, Dong-Yao Zhao, Bing Gao, Hai-Ning Zhou, Shi-Lin Gao, Lian-Feng Zhang

Erschienen in: Investigational New Drugs | Ausgabe 6/2019

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Summary

Background Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Novel anticancer drugs against gastric cancer are urgently needed. Methods Compound 10 was designed and synthesized via a molecular hybridization strategy based on the natural product formononetin. It was evaluated for their antiproliferative activity against three gastric cancer cell lines (SGC7901, MKN45 and MGC803). Results Derivative 10 displayed potently antiproliferative activity with an IC₅₀ value of 1.07 μM against SGC7901 cells. Derivative 10 could inhibit the growth and migration against gastric cancer SGC7901 cells through the Wnt/β-Catenin and AKT/mTOR pathways. From the in vivo expremints, it could effectively inhibited SGC7901 xenograft tumor growth in vivo without significant loss of the body weight. Conclusion Derivative 10 is an novel antitumor agent with potential for further clinical applications to treat gastric cancer.

Badgwell B, Blum M, Estrella J, Chiang Y-J, Das P, Matamoros A, Fournier K, Mansfield P, Ajani J (2015) Predictors of survival in patients with Resectable gastric Cancer treated with preoperative Chemoradiation therapy and gastrectomy. J Am Coll Surg 221(1):83–90. https://doi.org/10.1016/j.jamcollsurg.2015.04.004 CrossRefPubMed

Sun H, Ni S, Ye M, Weng W, Zhang Q, Zhang M, Tan C, Wang L, Huang D, Du X, Xu M, Sheng W (2018) Hedgehog interacting protein 1 is a prognostic marker and suppresses cell metastasis in gastric Cancer. J Cancer 9(24):4642–4649. https://doi.org/10.7150/jca.27686 CrossRefPubMedPubMedCentral

Chen X, Chen X, Zhang X, Wang L, Cao P, Rajamanickam V, Wu C, Zhou H, Cai Y, Liang G, Wang Y (2018) Curcuminoid B63 induces ROS-mediated paraptosis-like cell death by targeting TrxR1 in gastric cells. Redox Biol 21:101061–101061. https://doi.org/10.1016/j.redox.2018.11.019 CrossRefPubMedPubMedCentral

Wang H, Zhang D, Ge M, Li Z, Jiang J, Li Y (2015) Formononetin inhibits enterovirus 71 replication by regulating COX- 2/PGE₂ expression. Virol J 12:35–35. https://doi.org/10.1186/s12985-015-0264-x CrossRefPubMedPubMedCentral

Li S, Dang Y, Zhou X, Huang B, Huang X, Zhang Z, Kwan YW, Chan SW, Leung GPH, Lee SMY, Hoi MPM (2015) Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway. Sci Rep 5:16815–16815. https://doi.org/10.1038/srep16815 CrossRefPubMedPubMedCentral

Wu D, Wu K, Zhu Q, Xiao W, Shan Q, Yan Z, Wu J, Deng B, Xue Y, Gong W, Lu G, Ding Y (2018) Formononetin administration ameliorates dextran sulfate sodium-induced acute colitis by inhibiting NLRP3 Inflammasome signaling pathway. Mediat Inflamm 2018:3048532–3048532. https://doi.org/10.1155/2018/3048532 CrossRef

Chen J, Zeng J, Xin M, Huang W, Chen X (2011) Formononetin induces cell cycle arrest of human breast Cancer cells via IGF1/PI3K/Akt pathways in vitro and in vivo. Horm Metab Res 43(10):681–686. https://doi.org/10.1055/s-0031-1286306 CrossRefPubMed

Zhang X, Ni Q, Wang Y, Fan H, Li Y (2018) Synergistic anticancer effects of Formononetin and Temozolomide on glioma C6 cells. Biol Pharm Bull 41(8):1194–1202. https://doi.org/10.1248/bpb.b18-00002 CrossRefPubMed

Lee H, Lee D, Kang KS, Song JH, Choi Y-K (2018) Inhibition of intracellular ROS accumulation by Formononetin attenuates cisplatin-mediated apoptosis in LLC-PK1 cells. Int J Mol Sci 19(3):813. https://doi.org/10.3390/ijms19030813 CrossRefPubMedCentral

10.

Hwang JS, Kang ES, Han SG, Lim D-S, Paek KS, Lee C-H, Seo HG (2018) Formononetin inhibits lipopolysaccharide-induced release of high mobility group box 1 by upregulating SIRT1 in a PPARδ-dependent manner. Peer J 6:e4208–e4208. https://doi.org/10.7717/peerj.4208 CrossRefPubMed

11.

Yang Y, Zhao Y, Ai X, Cheng B, Lu S (2014) Formononetin suppresses the proliferation of human non-small cell lung cancer through induction of cell cycle arrest and apoptosis. Int J Clin Exp Pathol 7(12):8453–8461PubMedPubMedCentral

12.

Madadi NR, Penthala NR, Howk K, Ketkar A, Eoff RL, Borrelli MJ, Crooks PA (2015) Synthesis and biological evaluation of novel 4,5-disubstituted 2H-1,2,3-triazoles as cis-constrained analogues of combretastatin A-4. Eur J Med Chem 103:123–132. https://doi.org/10.1016/j.ejmech.2015.08.041 CrossRefPubMedPubMedCentral

13.

Xu G, Shi C, Guo D, Wang L, Ling Y, Han X, Luo J (2015) Functional-segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment. Acta Biomater 21:85–98. https://doi.org/10.1016/j.actbio.2015.04.021 CrossRefPubMedPubMedCentral

14.

Khan S, Malla AM, Zafar A, Naseem I (2017) Synthesis of novel coumarin nucleus-based DPA drug-like molecular entity: in vitro DNA/Cu(II) binding, DNA cleavage and pro-oxidant mechanism for anticancer action. PLoS One 12(8):e0181783–e0181783. https://doi.org/10.1371/journal.pone.0181783 CrossRefPubMedPubMedCentral

15.

Zhang R-R, Liu J, Zhang Y, Hou M-Q, Zhang M-Z, Zhou F, Zhang W-H (2016) Microwave-assisted synthesis and antifungal activity of novel coumarin derivatives: Pyrano[3,2-c]chromene-2,5-diones. Eur J Med Chem 116:76–83. https://doi.org/10.1016/j.ejmech.2016.03.069 CrossRef

16.

Yang H-L, Cai P, Liu Q-H, Yang X-L, Li F, Wang J, Wu J-J, Wang X-B, Kong L-Y (2017) Design, synthesis and evaluation of coumarin-pargyline hybrids as novel dual inhibitors of monoamine oxidases and amyloid-β aggregation for the treatment of Alzheimer's disease. Eur J Med Chem 138:715–728. https://doi.org/10.1016/j.ejmech.2017.07.008 CrossRefPubMed

17.

Cao D, Liu Y, Yan W, Wang C, Bai P, Wang T, Tang M, Wang X, Yang Z, Ma B, Ma L, Lei L, Wang F, Xu B, Zhou Y, Yang T, Chen L (2016) Design, synthesis, and evaluation of in vitro and in vivo anticancer activity of 4-substituted Coumarins: a novel class of potent tubulin polymerization inhibitors. J Med Chem 59(12):5721–5739. https://doi.org/10.1021/acs.jmedchem.6b00158 CrossRefPubMed

18.

Kakwani MD, Suryavanshi P, Ray M, Rajan MGR, Majee S, Samad A, Devarajan P, Degani MS (2011) Design, synthesis and antimycobacterial activity of cinnamide derivatives: a molecular hybridization approach. Bioorg Med Chem Lett 21(7):1997–1999. https://doi.org/10.1016/j.bmcl.2011.02.022 CrossRefPubMed

19.

Barbosa TP, Sousa SCO, Amorim FM, Rodrigues YKS, de Assis PAC, Caldas JPA, Oliveira MR, Vasconcellos MLAA (2011) Design, synthesis and antileishmanial in vitro activity of new series of chalcones-like compounds: a molecular hybridization approach. Bioorg Med Chem 19(14):4250–4256. https://doi.org/10.1016/j.bmc.2011.05.055 CrossRefPubMed

20.

Wang Y, Zhou Y, Zheng Z, Li J, Yan Y, Wu W (2018) Sulforaphane metabolites reduce resistance to paclitaxel via microtubule disruption. Cell Death Dis 9(11):1134. https://doi.org/10.1038/s41419-018-1174-9 CrossRefPubMedPubMedCentral

21.

Deng L, Gao X, Liu B, He X, Xu J, Qiang J, Wu Q, Liu S (2018) NMT1 inhibition modulates breast cancer progression through stress-triggered JNK pathway. Cell Death Dis 9(12):1143. https://doi.org/10.1038/s41419-018-1201-x CrossRefPubMedPubMedCentral

22.

Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA (2002) Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast Sir2 and human SIRT1. J Biol Chem 277(47):45099–45107CrossRef

23.

Feng Y, Wu J, Chen L, Luo C, Shen X, Chen K, Jiang H, Liu D (2009) A fluorometric assay of SIRT1 deacetylation activity through quantification of nicotinamide adenine dinucleotide. Anal Biochem 395(2):205–210. https://doi.org/10.1016/j.ab.2009.08.011 CrossRefPubMed

24.

Sophia J, Kowshik J, Dwivedi A, Bhutia SK, Manavathi B, Mishra R, Nagini S (2018) Nimbolide, a neem limonoid inhibits cytoprotective autophagy to activate apoptosis via modulation of the PI3K/Akt/GSK-3β signalling pathway in oral cancer. Cell Death Dis 9(11):1087. https://doi.org/10.1038/s41419-018-1126-4 CrossRefPubMedPubMedCentral

25.

Rivera-Reyes A, Ye S, Marino GE, Egolf S, Ciotti G, Chor S, Liu Y, Posimo JM, PMC P, Pak K, Babichev Y, Sostre-Colón J, Tameire F, Leli NM, Koumenis C, Brady DC, Mancuso A, Weber K, Gladdy R, Qi J, Eisinger-Mathason TSK (2018) YAP1 enhances NF-κB-dependent and independent effects on clock-mediated unfolded protein responses and autophagy in sarcoma. Cell Death Dis 9(11):1108. https://doi.org/10.1038/s41419-018-1142-4 CrossRefPubMedPubMedCentral

26.

Zhao Y, Liu Y, Lin L, Huang Q, He W, Zhang S, Dong S, Wen Z, Rao J, Liao W, Shi M (2018) The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1. Mol Cancer 17(1):69. https://doi.org/10.1186/s12943-018-0820-2 CrossRefPubMedPubMedCentral

27.

Hwang ES, Song SB (2017) Nicotinamide is an inhibitor of SIRT1 in vitro, but can be a stimulator in cells. Cell Mol Life Sci 74(18):3347–3362. https://doi.org/10.1007/s00018-017-2527-8 CrossRefPubMed

28.

Zhang W, Zhang Y, Guo X, Zeng Z, Wu J, Liu Y, He J, Wang R, Huang Q, Chen Z (2017) Sirt1 protects endothelial cells against LPS-induced barrier dysfunction. Oxidative Med Cell Longev 2017:4082102–4082102. https://doi.org/10.1155/2017/4082102 CrossRef

29.

Liu D, Li S, Gong L, Yang Y, Han Y, Xie M, Zhang C (2018) Suppression of microRNA-141 suppressed p53 to protect against neural apoptosis in epilepsy by SIRT1 expression. J Cell Biochem. https://doi.org/10.1002/jcb.28216 CrossRef

30.

Peck B, Chen C-Y, Ho K-K, Di Fruscia P, Myatt SS, Coombes RC, Fuchter MJ, Hsiao C-D, Lam EWF (2010) SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. Mol Cancer Ther 9(4):844–855CrossRef

31.

Vaziri H, Dessain SK, Eaton EN, Imai S-I, Frye RA, Pandita TK, Guarente L, Weinberg RA (2001) hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell 107(2):149–159. https://doi.org/10.1016/S0092-8674(01)00527-X CrossRefPubMed

32.

Maretzky T, Reiss K, Ludwig A, Buchholz J, Scholz F, Proksch E, de Strooper B, Hartmann D, Saftig P (2005) ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion, migration, and beta-catenin translocation. P Natl Acad Sci USA 102(26):9182–9187. https://doi.org/10.1073/pnas.0500918102 CrossRef

33.

Cai C, Zhu X (2012) The Wnt/β-catenin pathway regulates self-renewal of cancer stem-like cells in human gastric cancer. Mol Med Rep 5(5):1191PubMed

34.

Fodde R, Brabletz T (2007) Wnt/β-catenin signaling in cancer stemness and malignant behavior. Curr Opin Cell Biol 19(2):150–158. https://doi.org/10.1016/j.ceb.2007.02.007 CrossRefPubMed

35.

Li H, Zhang B, Liu Y, Yin C (2014) EBP50 inhibits the migration and invasion of human breast cancer cells via LIMK/cofilin and the PI3K/Akt/mTOR/MMP signaling pathway. Med Oncol 31(9):162. https://doi.org/10.1007/s12032-014-0162-x CrossRefPubMed

36.

Li H, Zeng J, Shen K (2014) PI3K/AKT/mTOR signaling pathway as a therapeutic target for ovarian cancer. Arch Gynecol Obstet 290(6):1067–1078. https://doi.org/10.1007/s00404-014-3377-3 CrossRefPubMed

37.

Demirci S, Doğan A, Apdik H, Tuysuz EC, Gulluoglu S, Bayrak OFS, Şahin F (2018) Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells. Mol Cell Biochem 437(1):133–142. https://doi.org/10.1007/s11010-017-3101-2 CrossRefPubMed

Titel: Discovery and anticancer evaluation of a formononetin derivative against gastric cancer SGC7901 cells
verfasst von: Jian-Ning Yao
Xue-Xiu Zhang
Yan-Zhen Zhang
Jia-Heng Li
Dong-Yao Zhao
Bing Gao
Hai-Ning Zhou
Shi-Lin Gao
Lian-Feng Zhang
Publikationsdatum: 30.03.2019
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 6/2019
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-019-00767-7

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Discovery and anticancer evaluation of a formononetin derivative against gastric cancer SGC7901 cells

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