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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Exploration of the Mechanism of Kaempferol in the Treatment of Cervical Cancer-based on Metabolomics and Network Pharmacology

Author(s): Dong-Min Cao* and Tao Liu

Volume 29, Issue 36, 2023

Published on: 07 December, 2023

Page: [2877 - 2890] Pages: 14

DOI: 10.2174/0113816128268061231012073704

Price: $65

Abstract

Background: Cervical cancer is a prevalent malignancy among women globally.

Objective: We aimed to uncover the mechanism of action of kaempferol in the treatment of cervical cancer using an integrated approach that combines metabolomics with network pharmacology.

Methods: Initially, we investigated the specific metabolites and potential pathways influenced by kaempferol in the pathological progression of cervical cancer, employing UHPLC-Q-Orbitrap MS metabolomics. In addition, network pharmacology analysis was performed to ascertain the pivotal targets of kaempferol in the context of CC therapy.

Results: Metabolomics analysis indicated that the therapeutic effect of kaempferol on cervical cancer is primarily associated with 11 differential metabolites and 7 metabolite pathways. These pathways include arginine and proline metabolism, the tricarboxylic acid cycle, phenylalanine, tyrosine, and tryptophan biosynthesis, fatty acid biosynthesis, glycerophospholipid metabolism, pantothenate and CoA biosynthesis, and tyrosine metabolism. Additionally, kaempferol was found to regulate 3 differential metabolites, namely palmitic acid, citric acid, and L-tyrosine, by directly targeting 7 specific proteins, including AKR1B1, CS, EGFR, PLA2G1B, PPARG, SLCO2B1, and SRC. Furthermore, molecular docking demonstrated strong binding affinities between kaempferol and 7 crucial targets.

Conclusion: This study elucidates the intricate mechanisms by which kaempferol acts against cervical cancer. Furthermore, this research offers a novel approach to investigating the potential pharmacological mechanisms of action exhibited by natural compounds.

« Previous Next »
[1]
Liu C, Li X, Huang Q, et al. Single-cell RNA-sequencing reveals radiochemotherapy-induced innate immune activation and MHC-II upregulation in cervical cancer. Signal Transduct Target Ther 2023; 8(1): 44.
[http://dx.doi.org/10.1038/s41392-022-01264-9] [PMID: 36710358]
[2]
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[3]
Guo Q, Sun Y, Kong E, et al. Apatinib combined with chemotherapy or concurrent chemo-brachytherapy in patients with recurrent or advanced cervical cancer. Medicine (Baltimore) 2020; 99(11): e19372.
[http://dx.doi.org/10.1097/MD.0000000000019372] [PMID: 32176061]
[4]
Gwacham NI, McKenzie ND, Fitzgerald ER, Ahmad S, Holloway RW. Neoadjuvant chemotherapy followed by fertility sparing surgery in cervical cancers size 2–4 cm; Emerging data and future perspectives. Gynecol Oncol 2021; 162(3): 809-15.
[http://dx.doi.org/10.1016/j.ygyno.2021.06.006] [PMID: 34130862]
[5]
Gairola K, Gururani S, Bahuguna A, Garia V, Pujari R, Dubey SK. Natural products targeting cancer stem cells: Implications for cancer chemoprevention and therapeutics. J Food Biochem 2021; 45(7): e13772.
[http://dx.doi.org/10.1111/jfbc.13772] [PMID: 34028051]
[6]
Ma L, Zhang M, Zhao R, Wang D, Ma Y, Ai L. Plant natural products: Promising resources for cancer chemoprevention. Molecules 2021; 26(4): 933.
[http://dx.doi.org/10.3390/molecules26040933] [PMID: 33578780]
[7]
Sharifi-Rad M, Fokou P, Sharopov F, et al. Antiulcer agents: From plant extracts to phytochemicals in healing promotion. Molecules 2018; 23(7): 1751.
[http://dx.doi.org/10.3390/molecules23071751] [PMID: 30018251]
[8]
Rajendran P, Rengarajan T, Nandakumar N, Palaniswami R, Nishigaki Y, Nishigaki I. Kaempferol, a potential cytostatic and cure for inflammatory disorders. Eur J Med Chem 2014; 86: 103-12.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.011] [PMID: 25147152]
[9]
Imran M, Salehi B, Sharifi-Rad J, et al. Kaempferol: A key emphasis to its anticancer potential. Molecules 2019; 24(12): 2277.
[http://dx.doi.org/10.3390/molecules24122277] [PMID: 31248102]
[10]
Wang J, Fang X, Ge L, et al. Antitumor, antioxidant and anti-inflammatory activities of kaempferol and its corresponding glycosides and the enzymatic preparation of kaempferol. PLoS One 2018; 13(5): e0197563.
[http://dx.doi.org/10.1371/journal.pone.0197563] [PMID: 29771951]
[11]
Pei J, Chen A, Zhao L, Cao F, Ding G, Xiao W. One-pot synthesis of hyperoside by a three-enzyme cascade using a UDP-galactose regeneration system. J Agric Food Chem 2017; 65(29): 6042-8.
[http://dx.doi.org/10.1021/acs.jafc.7b02320] [PMID: 28660766]
[12]
Hung TW, Chen PN, Wu HC, et al. Kaempferol inhibits the invasion and migration of renal cancer cells through the downregulation of AKT and FAK pathways. Int J Med Sci 2017; 14(10): 984-93.
[http://dx.doi.org/10.7150/ijms.20336] [PMID: 28924370]
[13]
Liao W, Chen L, Ma X, Jiao R, Li X, Wang Y. Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells. Eur J Med Chem 2016; 114: 24-32.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.045] [PMID: 26974372]
[14]
Tu LY, Bai HH, Cai JY, Deng SP. The mechanism of kaempferol induced apoptosis and inhibited proliferation in human cervical cancer SiHa cell: From macro to nano. Scanning 2016; 38(6): 644-53.
[http://dx.doi.org/10.1002/sca.21312] [PMID: 26890985]
[15]
Wang X, Zhang A, Sun H. Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma. Hepatology 2013; 57(5): 2072-7.
[http://dx.doi.org/10.1002/hep.26130] [PMID: 23150189]
[16]
Gutschmann B, Bock MCE, Jahns S, Neubauer P, Brigham CJ, Riedel SL. Untargeted metabolomics analysis of Ralstonia eutropha during plant oil cultivations reveals the presence of a fucose salvage pathway. Sci Rep 2021; 11(1): 14267.
[http://dx.doi.org/10.1038/s41598-021-93720-9] [PMID: 34253787]
[17]
Hopkins AL. Network pharmacology: The next paradigm in drug discovery. Nat Chem Biol 2008; 4(11): 682-90.
[http://dx.doi.org/10.1038/nchembio.118] [PMID: 18936753]
[18]
Tao Q, Du J, Li X, et al. Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19. Drug Dev Ind Pharm 2020; 46(8): 1345-53.
[http://dx.doi.org/10.1080/03639045.2020.1788070] [PMID: 32643448]
[19]
Morris GM, Huey R, Lindstrom W, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 2009; 30(16): 2785-91.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[20]
Eniafe J, Jiang S. The functional roles of TCA cycle metabolites in cancer. Oncogene 2021; 40(19): 3351-63.
[http://dx.doi.org/10.1038/s41388-020-01639-8] [PMID: 33864000]
[21]
Peng M, Yang D, Hou Y, et al. Intracellular citrate accumulation by oxidized ATM-mediated metabolism reprogramming via PFKP and CS enhances hypoxic breast cancer cell invasion and metastasis. Cell Death Dis 2019; 10(3): 228.
[http://dx.doi.org/10.1038/s41419-019-1475-7] [PMID: 30850587]
[22]
Zhu S, Jiao W, Xu Y, et al. Palmitic acid inhibits prostate cancer cell proliferation and metastasis by suppressing the PI3K/Akt pathway. Life Sci 2021; 286: 120046.
[http://dx.doi.org/10.1016/j.lfs.2021.120046] [PMID: 34653428]
[23]
Binker-Cosen MJ, Richards D, Oliver B, Gaisano HY, Binker MG, Cosen-Binker LI. Palmitic acid increases invasiveness of pancreatic cancer cells AsPC-1 through TLR4/ROS/NF-κB/MMP-9 signaling pathway. Biochem Biophys Res Commun 2017; 484(1): 152-8.
[http://dx.doi.org/10.1016/j.bbrc.2017.01.051] [PMID: 28088520]
[24]
Khan I, Nam M, Kwon M, et al. LC/MS-based polar metabolite profiling identified unique biomarker signatures for cervical cancer and cervical intraepithelial neoplasia using global and targeted metabolomics. Cancers (Basel) 2019; 11(4): 511.
[http://dx.doi.org/10.3390/cancers11040511] [PMID: 30974861]
[25]
Citri A, Yarden Y. EGF-ERBB signalling: Towards the systems level. Nat Rev Mol Cell Biol 2006; 7(7): 505-16.
[http://dx.doi.org/10.1038/nrm1962] [PMID: 16829981]
[26]
He C, Mao D, Hua G, et al. The Hippo/ YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression. EMBO Mol Med 2015; 7(11): 1426-49.
[http://dx.doi.org/10.15252/emmm.201404976] [PMID: 26417066]
[27]
Ji J, Xu MX, Qian TY, et al. The AKR1B1 inhibitor epalrestat suppresses the progression of cervical cancer. Mol Biol Rep 2020; 47(8): 6091-103.
[http://dx.doi.org/10.1007/s11033-020-05685-z] [PMID: 32761301]

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