A network pharmacology-based study on the molecular mechanisms of the active ingredients of Cannabis sativa L. against multidrug resistance in cervical cancer

IM Mangoato; A Shcherbakova; M G Matsabisa; G Ulrich-Merzenich

doi:10.1055/s-0042-1749282

Zeitschrift für Phytotherapie, Table of Contents

Zeitschrift für Phytotherapie 2022; 43(S 01): S44
DOI: 10.1055/s-0042-1749282

Abstracts Poster | Phytotherapie 2022 – innovativ

A network pharmacology-based study on the molecular mechanisms of the active ingredients of Cannabis sativa L. against multidrug resistance in cervical cancer

Authors

IM Mangoato

¹Indegenous Knowledge Systems Unit, Department of Pharmacology, University of the Free State, South Africa

²AG Synergy Research & Experimental Medicine, Medical Clinic III, University Hospital Bonn (UKB), Germany
A Shcherbakova

²AG Synergy Research & Experimental Medicine, Medical Clinic III, University Hospital Bonn (UKB), Germany
M G Matsabisa

¹Indegenous Knowledge Systems Unit, Department of Pharmacology, University of the Free State, South Africa
G Ulrich-Merzenich

²AG Synergy Research & Experimental Medicine, Medical Clinic III, University Hospital Bonn (UKB), Germany

Abstract

Full Text

Introduction There is an increasing need to develop novel adjunctive therapeutic agents against multidrug resistance (MDR) in cervical cancer from natural products due to chemoresistance in the current treatment.

Aim To explore the potential targets and mechanisms of the active ingredients of C. sativa L. against MDR in cervical cancer by network pharmacology.

Methods C. sativa L. inflorescences were extracted in cold ethanol and fractionated by hydro distillation. Potential targets of C. sativa L. active ingredients, cisplatin (DDP), the disease and cervical cancer cells (HeLa and CaSki) were obtained from various databases. The compound-target network and protein-protein interaction (PPI) analysis were built using the Cytoscape platform and STRING database, respectively. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed on the hub genes using NetworkAnalyst. Experimentally, CaSki/DDP and HeLa/DDP cells were developed by incremental administration of DDP in vitro. Cell viability of parental and DDP-resistant cells was evaluated using resazurin assay.

Results A total of 1026 disease, 201 HeLa, 31 CaSki and 116 cisplatin-associated targets were identified of which 53 were drug-disease intersection targets. PPI network analysis yielded 17 cannabinoids and 2 terpene target hub genes. KEGG analysis revealed that these hub genes were involved in a variety of oncogenic signalling pathways while 792 GO biological processes were summarized. Resistant cell lines were successfully established and IC₅₀ values in all cell lines obtained at 24 h and 48 h.

Conclusion This study using in silico network pharmacology provides a comprehensive insight into potential target genes and underlying mechanisms by which C. sativa L. might modulate MDR in cervical cancer.