Mechanistic elucidation of Juglanthraquinone C targeting breast Cancer: A network Pharmacology-based investigation

Hina Qayoom; Mustfa Alkhanani; Abdullah Almilaibary; Suliman A Alsagaby; Manzoor Ahmad Mir

doi:10.1016/j.sjbs.2023.103705

Mechanistic elucidation of Juglanthraquinone C targeting breast Cancer: A network Pharmacology-based investigation

Saudi J Biol Sci. 2023 Jul;30(7):103705. doi: 10.1016/j.sjbs.2023.103705. Epub 2023 Jun 15.

Authors

Hina Qayoom¹, Mustfa Alkhanani², Abdullah Almilaibary³, Suliman A Alsagaby⁴, Manzoor Ahmad Mir¹

Affiliations

¹ Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar 190006, India.
² Department of Family and Community Medicine, Faculty of Medicine, Al Baha University, Albaha 65511, KSA.
³ Department of Biology, College of Science, Hafr Al Batin University of Hafr Al-Batin, 31991, KSA.
⁴ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, AL-Majmaah 11932, KSA.

Abstract

Breast cancer is the leading cause of death among women worldwide. Despite the recent treatment options like surgery, chemotherapy etc. the lethality of breast cancer is alarming. Natural compounds are considered a better treatment option against breast carcinoma because of their lower side effects and specificity in targeting important proteins involved in the aberrant activation of pathways in breast cancer. A recently discovered compound called Juglanthraquinone C, which is found in the bark of the Juglans mandshurica Maxim (Juglandaceae) tree has shown promising cytotoxicity in hepatocellular carcinoma. However, not much data is available on the molecular mechanisms followed by this compound. Therefore, we aimed to investigate the molecular mechanism followed by Juglanthraquinone C against breast cancer. We used the network pharmacology technique to analyse the mechanism of action of Juglanthraquinone C in breast cancer and validated our study by applying various computational tools such as UALCAN, cBioportal, TIMER, docking and simulation. The results showed the compound and breast cancer target network shared 31 common targets. Moreover, we observed that Juglanthraquinone C targets multiple deregulated genes in breast cancer such as TP53, TGIF1, IGF1R, SMAD3, JUN, CDC42, HBEGF, FOS and signaling pathways such as PI3K-Akt pathway, TGF-β signaling pathway, MAPK pathway and HIPPO signaling pathway. A docking examination revealed that the investigated drug had a high affinity for the primary target TGIF1 protein. A stable protein-ligand combination was generated by the best hit molecule, according to molecular dynamics modeling. The main aim of this study was to examine Juglanthraquinone C's significance as a prospective breast cancer treatment and to better understand the molecular mechanism this substance uses in breast cancer since there is a need to discover new therapeutics to decrease the load on current therapeutics which also are currently ineffective due to several side effects and development of drug resistance.

Keywords: Breast cancer; Docking and Simulation; Juglanthraquinone C; Network pharmacology.