Exploring the Anticancer Potential of : A Systematic Network Pharmacology Study on Lung Cancer

Overview

Journal J Adv Pharm Technol Res

Date 2024 Feb 23

PMID 38389971

Authors

Roihatul Mutiah

Ermin Rachmawati

Affiliations

Soon will be listed here.

Abstract

Chemotherapy application in lung cancer patients has several side effects and shows lower effectiveness due to chemoresistance. Although (Mill.) Urb. (EBE) elicit anticancer properties, yet the exact profile of its active compounds and lung cancer inhibition mechanisms were not fully understood. This study aimed to identify suggestive compounds from EBE extract and explain the molecular mechanisms of EBE against lung cancer. Identification of the compound from the EBE extract was confirmed using liquid chromatography-tandem mass spectrophotometry (LC-MS/MS). The bioavailability profile of three major metabolites was identified using absorption, distribution, metabolism, excretion, toxicity software. The anticancer molecular mechanism prediction of the drugs was ascertained by network pharmacology using Cytoscape 3.9.1 and the protein-protein interaction network technique with STRING 11.0. Interaction between resveratrol and extracellular growth factor receptor (EGFR) was analyzed using site-specific molecular docking with erlotinib as the control using PyRx Autodock Vina 9.0 and BIOVIA Discovery Studio. A total of 16 active compounds were identified from LC-MS/MS. Only resveratrol showed anticancer properties by its interaction with 13 genes and 6 signaling pathways related to lung cancer. The molecular docking result supports the network pharmacology finding. The binding affinity of resveratrol with EGFR, important receptor in lung cancer, was more negative (-6.9 kcal/mol) than erlotinib (-6.2 kcal/mol) as the control. Evidence suggested that resveratrol in EBE exhibits anticancer effects by modulating lung cancer cell proliferation and apoptosis through EGFR binding.

References

Liu X, Wu J, Zhang D, Wang K, Duan X, Zhang X . A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Willd. on Colorectal Cancer. Evid Based Complement Alternat Med. 2018; 2018:6517034. PMC: 5829364. DOI: 10.1155/2018/6517034. View

Ashrafizadeh M, Zarrabi A, Hushmandi K, Hashemi F, Moghadam E, Owrang M . Lung cancer cells and their sensitivity/resistance to cisplatin chemotherapy: Role of microRNAs and upstream mediators. Cell Signal. 2020; 78:109871. DOI: 10.1016/j.cellsig.2020.109871. View

Mutiah R, Sari R, Firsyaradha W, Listiyana A, Indrawijaya Y, Wafi A . Activity and Toxicity of Eleutherine palmifolia (L.) Merr. Extract on BALB/c Mice Colitis-Associated Colon Cancer Model. Asian Pac J Cancer Prev. 2020; 21(12):3579-3586. PMC: 8046305. DOI: 10.31557/APJCP.2020.21.12.3579. View

Li W, Li C, Ma L, Jin F . Resveratrol inhibits viability and induces apoptosis in the small‑cell lung cancer H446 cell line via the PI3K/Akt/c‑Myc pathway. Oncol Rep. 2020; 44(5):1821-1830. PMC: 7550979. DOI: 10.3892/or.2020.7747. View

Tartour E, Zitvogel L . Lung cancer: potential targets for immunotherapy. Lancet Respir Med. 2014; 1(7):551-63. DOI: 10.1016/S2213-2600(13)70159-0. View

Li L, Chong Q, Wang L, Cher G, Soo R . Different treatment efficacies and side effects of cytotoxic chemotherapy. J Thorac Dis. 2020; 12(7):3785-3795. PMC: 7399437. DOI: 10.21037/jtd.2019.08.63. View

Rasheduzzaman M, Jeong J, Park S . Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-κB signaling. Life Sci. 2018; 208:208-220. DOI: 10.1016/j.lfs.2018.07.035. View

Ieyama T, Gunawan-Puteri M, Kawabata J . α-Glucosidase inhibitors from the bulb of Eleutherine americana. Food Chem. 2014; 128(2):308-11. DOI: 10.1016/j.foodchem.2011.03.021. View

Khan K, Quispe C, Javed Z, Iqbal M, Sadia H, Raza S . Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer. Cancer Cell Int. 2020; 20(1):560. PMC: 7685642. DOI: 10.1186/s12935-020-01660-7. View

10.

Aungst B . Optimizing Oral Bioavailability in Drug Discovery: An Overview of Design and Testing Strategies and Formulation Options. J Pharm Sci. 2016; 106(4):921-929. DOI: 10.1016/j.xphs.2016.12.002. View

11.

Wright C, Iyer A, Yakisich J, Azad N . Anti-Tumorigenic Effects of Resveratrol in Lung Cancer Cells Through Modulation of c-FLIP. Curr Cancer Drug Targets. 2017; 17(7):669-680. PMC: 6476192. DOI: 10.2174/1568009617666170315162932. View

12.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

13.

He Z, Gao K, Dong L, Liu L, Qu X, Zou Z . Drug screening and biomarker gene investigation in cancer therapy through the human transcriptional regulatory network. Comput Struct Biotechnol J. 2023; 21:1557-1572. PMC: 9984461. DOI: 10.1016/j.csbj.2023.02.005. View

14.

Huang D, Sherman B, Lempicki R . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2008; 37(1):1-13. PMC: 2615629. DOI: 10.1093/nar/gkn923. View

15.

Poornima P, Kumar J, Zhao Q, Blunder M, Efferth T . Network pharmacology of cancer: From understanding of complex interactomes to the design of multi-target specific therapeutics from nature. Pharmacol Res. 2016; 111:290-302. DOI: 10.1016/j.phrs.2016.06.018. View

16.

Hao X, Han F, Zhang N, Chen H, Jiang X, Yin L . TC2N, a novel oncogene, accelerates tumor progression by suppressing p53 signaling pathway in lung cancer. Cell Death Differ. 2018; 26(7):1235-1250. PMC: 6748156. DOI: 10.1038/s41418-018-0202-8. View

17.

Iqbal M, Arora S, Prakasam G, Calin G, Syed M . MicroRNA in lung cancer: role, mechanisms, pathways and therapeutic relevance. Mol Aspects Med. 2018; 70:3-20. DOI: 10.1016/j.mam.2018.07.003. View

18.

Yang Q, Xu E, Dai J, Liu B, Han Z, Wu J . A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015; 285(2):79-88. DOI: 10.1016/j.taap.2015.04.003. View