Unraveling the molecular mechanism of l-menthol against cervical cancer based on network pharmacology, molecular docking and in vitro analysis

被引：10

作者：

Sidhu, Harsimran ^{[1
]}

Gautam, Lalit Kumar ^{[1
]}

Capalash, Neena ^{[1
]}

机构：

[1] Panjab Univ, Dept Biotechnol, Basic Med Sci Block 1,Sect 25, Chandigarh 160014, India

来源：

MOLECULAR DIVERSITY | 2023年 / 27卷 / 01期

关键词：

l-menthol; Network pharmacology; Anti-proliferation; Apoptosis; Anti-metastasis; Cervical cancer; BREAST-CANCER; CELL-DEATH; DRUG; PROLIFERATION; APOPTOSIS; THERAPEUTICS; ACTIVATION; EXPRESSION;

D O I：

10.1007/s11030-022-10429-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cervical cancer is a major cause of gynecological related mortalities in developing countries. Cisplatin, a potent chemotherapeutic agent used for treating advanced cervical cancer exhibits side effects and resistance development. The current study was aimed to investigate the repurposing of 1-menthol as a potential therapeutic drug against cervical cancer. L-menthol was predicted to be non-toxic with good pharmacokinetic properties based on SwissADME and pkCSM analysis. Subsequently, 543 and 1664 targets of 1-menthol and cervical cancer were identified using STITCH, BATMAN-TCM, PharmMapper and CTD databases. STRING and Cytoscape analysis of the merged protein-protein interaction network revealed 107 core targets of 1- menthol against cervical cancer. M-CODE identified highly connected clusters between the core targets which through KEGG analysis were found to be enriched in pathways related to apoptosis and adherence junctions. Molecular docking showed that 1- menthol targeted E6, E6AP and E7 onco-proteins of HPV that interact and inactivate TP53 and Rbl in cervical cancer, respectively. Molecular docking also showed good binding affinity of 1-menthol toward proteins associated with apoptosis and migration. Molecular dynamics simulation confirmed stability of the docked complexes. In vitro analysis confirmed that 1-menthol was cytotoxic towards cervical cancer CaSki cells and altered expression of TP53, Rb1, CDKN1A, E2F1, NFKB1, Akt-1, caspase-3, CDH1 and MMP-2 genes identified through network pharmacology approach. [GRAPHICS] .

引用

页码：323 / 340

页数：18

共 93 条

[1] Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers [J].

Abraham, Mark James ;

Murtola, Teemu ;

Schulz, Roland ;

Páll, Szilárd ;

Smith, Jeremy C. ;

Hess, Berk ;

Lindah, Erik .

SoftwareX, 2015, 1-2 :19-25

[2] Phytochemistry, Bioactivities, Pharmacokinetics and Toxicity Prediction of Selaginella repanda with Its Anticancer Potential against Human Lung, Breast and Colorectal Carcinoma Cell Lines [J].

Adnan, Mohd ;

Siddiqui, Arif Jamal ;

Hamadou, Walid Sabri ;

Patel, Mitesh ;

Ashraf, Syed Amir ;

Jamal, Arshad ;

Awadelkareem, Amir Mahgoub ;

Sachidanandan, Manojkumar ;

Snoussi, Mejdi ;

De Feo, Vincenzo .

MOLECULES, 2021, 26 (03)

[3] Ellagic Acid, Kaempferol, and Quercetin from Acacia nilotica: Promising Combined Drug With Multiple Mechanisms of Action [J].

Al-Nour M.Y. ;

Ibrahim M.M. ;

Elsaman T. .

Current Pharmacology Reports, 2019, 5 (4) :255-280

[4]

[Anonymous], 2012, The adverse outcome pathway for skin sensitisation initiated by covalent binding to proteins

[5] Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis [J].

Arbyn, Marc ;

Weiderpass, Elisabete ;

Bruni, Laia ;

de Sanjose, Silvia ;

Saraiya, Mona ;

Ferlay, Jacques ;

Bray, Freddie .

LANCET GLOBAL HEALTH, 2020, 8 (02) :E191-E203

[6] Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action [J].

Aung, Thazin Nwe ;

Qu, Zhipeng ;

Kortschak, R. Daniel ;

Adelson, David L. .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (03)

[7] Elimination of cervical cancer: challenges for developing countries [J].

Beddoe, Ann Marie .

ECANCERMEDICALSCIENCE, 2019, 13

[8] p53-dependent gene repression through p21 is mediated by recruitment of E2F4 repression complexes [J].

Benson, E. K. ;

Mungamuri, S. K. ;

Attie, O. ;

Kracikova, M. ;

Sachidanandam, R. ;

Manfredi, J. J. ;

Aaronson, S. A. .

ONCOGENE, 2014, 33 (30) :3959-3969

[9] let-7i-5p, miR-181a-2-3p and EGF/PI3K/SOX2 axis coordinate to maintain cancer stem cell population in cervical cancer [J].

Chhabra, Ravindresh .

SCIENTIFIC REPORTS, 2018, 8

[10] Changing neighbours, changing behaviour: cell adhesion molecule-mediated signalling during tumour progression [J].

Christofori, G .

EMBO JOURNAL, 2003, 22 (10) :2318-2323

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