Details

Autor(en) / Beteiligte

• Qayoom, Hina
• Alkhanani, Mustfa
• Almilaibary, Abdullah
• Alsagaby, Suliman A.
• Mir, Manzoor Ahmad

Titel

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

Ist Teil von

• Saudi journal of biological sciences, 2023-07, Vol.30 (7), p.103705-103705, Article 103705

Ort / Verlag

Saudi Arabia: Elsevier B.V

Erscheinungsjahr

2023

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• [Display omitted] •Due to limited efficacy, side effects and development of resistance against current chemotherapy there is a need for developing targeted therapy and one such promising approach is the exploration of natural compounds through cost-effective and less time-consuming computational tools such as network pharmacology and molecular docking and simulation studies.•On screening we found one such natural compound Juglanthraquinone C which has revealed promising prospective as an anti-cancer agent in breast carcinoma due to its ability to reduce inflammation, inhibit tumor growth, and suppress metastasis, as well as its synergistic effects with chemotherapy, which makes it a promising candidate for breast cancer treatment.•By using the network pharmacology and other in silico approaches we for the first time revealed the potential therapeutic targets of this compound in breast carcinoma and found that the compound and breast carcinoma target network shared 31 common targets. 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 ofJuglanthraquinone Cin 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 thatJuglanthraquinone 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.