Discovery and Anticancer Evaluation of a Formononetin Derivative Against Gastric Cancer SGC7901 Cells

Overview

Journal Invest New Drugs

Publisher Springer

Specialty Oncology

Date 2019 Apr 1

PMID 30929157

Citations 12

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 IC 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. Graphical abstract.

Citing Articles

Isoflavones: Promising Natural Agent for Cancer Prevention and Treatment.

Ul Hassan M, Shahbaz M, Imran M, Momal U, Naeem H, Mujtaba A Food Sci Nutr. 2025; 13(3):e70091.

PMID: 40078339 PMC: 11896816. DOI: 10.1002/fsn3.70091.

Isoflavone Derivatives as Potential Anticancer Agents: Synthesis and Bioactivity Studies.

Selepe M ChemMedChem. 2024; 19(23):e202400420.

PMID: 39091268 PMC: 11617652. DOI: 10.1002/cmdc.202400420.

Flavonoids and Gastric Cancer Therapy: From Signaling Pathway to Therapeutic Significance.

Cai J, Tan X, Hu Q, Pan H, Zhao M, Guo C Drug Des Devel Ther. 2024; 18:3233-3253.

PMID: 39081701 PMC: 11287762. DOI: 10.2147/DDDT.S466470.

Latest developments in coumarin-based anticancer agents: mechanism of action and structure-activity relationship studies.

Koley M, Han J, Soloshonok V, Mojumder S, Javahershenas R, Makarem A RSC Med Chem. 2024; 15(1):10-54.

PMID: 38283214 PMC: 10809357. DOI: 10.1039/d3md00511a.

A review of the botany, phytochemistry, traditional uses, pharmacology, toxicology, and quality control of the .

Wang P, Wang Z, Zhang Z, Cao H, Kong L, Ma W Front Pharmacol. 2023; 14:1242318.

PMID: 37680711 PMC: 10482111. DOI: 10.3389/fphar.2023.1242318.

References

Badgwell B, Blum M, Estrella J, Chiang Y, Das P, Matamoros A . Predictors of Survival in Patients with Resectable Gastric Cancer Treated with Preoperative Chemoradiation Therapy and Gastrectomy. J Am Coll Surg. 2015; 221(1):83-90. DOI: 10.1016/j.jamcollsurg.2015.04.004. View

Sun H, Ni S, Ye M, Weng W, Zhang Q, Zhang M . Hedgehog Interacting Protein 1 is a Prognostic Marker and Suppresses Cell Metastasis in Gastric Cancer. J Cancer. 2018; 9(24):4642-4649. PMC: 6299386. DOI: 10.7150/jca.27686. View

Chen X, Chen X, Zhang X, Wang L, Cao P, Rajamanickam V . Curcuminoid B63 induces ROS-mediated paraptosis-like cell death by targeting TrxR1 in gastric cells. Redox Biol. 2018; 21:101061. PMC: 6306695. DOI: 10.1016/j.redox.2018.11.019. View

Wang H, Zhang D, Ge M, Li Z, Jiang J, Li Y . Formononetin inhibits enterovirus 71 replication by regulating COX- 2/PGE₂ expression. Virol J. 2015; 12:35. PMC: 4351682. DOI: 10.1186/s12985-015-0264-x. View

Li S, Dang Y, Zhou X, Huang B, Huang X, Zhang Z . Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway. Sci Rep. 2015; 5:16815. PMC: 4645220. DOI: 10.1038/srep16815. View

Chen J, Zeng J, Xin M, Huang W, Chen X . Formononetin induces cell cycle arrest of human breast cancer cells via IGF1/PI3K/Akt pathways in vitro and in vivo. Horm Metab Res. 2011; 43(10):681-6. DOI: 10.1055/s-0031-1286306. View

Zhang X, Ni Q, Wang Y, Fan H, Li Y . Synergistic Anticancer Effects of Formononetin and Temozolomide on Glioma C6 Cells. Biol Pharm Bull. 2018; 41(8):1194-1202. DOI: 10.1248/bpb.b18-00002. View

Hwang J, Kang E, Han S, Lim D, Paek K, Lee C . Formononetin inhibits lipopolysaccharide-induced release of high mobility group box 1 by upregulating SIRT1 in a PPARδ-dependent manner. PeerJ. 2018; 6:e4208. PMC: 5756453. DOI: 10.7717/peerj.4208. View

Yang Y, Zhao Y, Ai X, Cheng B, Lu S . Formononetin suppresses the proliferation of human non-small cell lung cancer through induction of cell cycle arrest and apoptosis. Int J Clin Exp Pathol. 2015; 7(12):8453-61. PMC: 4313991. View

10.

Madadi N, Penthala N, Howk K, Ketkar A, Eoff R, Borrelli M . 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. 2015; 103:123-32. PMC: 4631050. DOI: 10.1016/j.ejmech.2015.08.041. View

11.

Xu G, Shi C, Guo D, Wang L, Ling Y, Han X . Functional-segregated coumarin-containing telodendrimer nanocarriers for efficient delivery of SN-38 for colon cancer treatment. Acta Biomater. 2015; 21:85-98. PMC: 4446163. DOI: 10.1016/j.actbio.2015.04.021. View

12.

Khan S, Malla A, Zafar A, Naseem I . 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. 2017; 12(8):e0181783. PMC: 5538679. DOI: 10.1371/journal.pone.0181783. View

13.

Yang H, Cai P, Liu Q, Yang X, Li F, Wang J . 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. 2017; 138:715-728. DOI: 10.1016/j.ejmech.2017.07.008. View

14.

Cao D, Liu Y, Yan W, Wang C, Bai P, Wang T . 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. 2016; 59(12):5721-39. DOI: 10.1021/acs.jmedchem.6b00158. View

15.

Kakwani M, Suryavanshi P, Ray M, Rajan M, Majee S, Samad A . Design, synthesis and antimycobacterial activity of cinnamide derivatives: a molecular hybridization approach. Bioorg Med Chem Lett. 2011; 21(7):1997-9. DOI: 10.1016/j.bmcl.2011.02.022. View

16.

Barbosa T, Sousa S, Amorim F, Rodrigues Y, de Assis P, Caldas J . Design, synthesis and antileishmanial in vitro activity of new series of chalcones-like compounds: a molecular hybridization approach. Bioorg Med Chem. 2011; 19(14):4250-6. DOI: 10.1016/j.bmc.2011.05.055. View

17.

Wang Y, Zhou Y, Zheng Z, Li J, Yan Y, Wu W . Sulforaphane metabolites reduce resistance to paclitaxel via microtubule disruption. Cell Death Dis. 2018; 9(11):1134. PMC: 6235886. DOI: 10.1038/s41419-018-1174-9. View

18.

Deng L, Gao X, Liu B, He X, Xu J, Qiang J . NMT1 inhibition modulates breast cancer progression through stress-triggered JNK pathway. Cell Death Dis. 2018; 9(12):1143. PMC: 6240078. DOI: 10.1038/s41419-018-1201-x. View

19.

Feng Y, Wu J, Chen L, Luo C, Shen X, Chen K . A fluorometric assay of SIRT1 deacetylation activity through quantification of nicotinamide adenine dinucleotide. Anal Biochem. 2009; 395(2):205-10. DOI: 10.1016/j.ab.2009.08.011. View

20.

Sophia J, Kowshik J, Dwivedi A, Bhutia S, Manavathi B, Mishra R . 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. 2018; 9(11):1087. PMC: 6199248. DOI: 10.1038/s41419-018-1126-4. View