Integrative Network Pharmacology of Moringa oleifera Combined with Gemcitabine against Pancreatic Cancer

Nursaffa Alisya Sahruddin,Norsyasya Adriana Rosdi,Sudha Warrier,Zhong Sun,Karuppiah Thilakavathy

doi:10.3390/pr9101742

Nursaffa Alisya Sahruddin, Norsyasya Adriana Rosdi + Show 3 more

Open Access

https://doi.org/10.3390/pr9101742

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Abstract

Gemcitabine (GEM) is the first-line chemotherapy drug for patients with advanced pancreatic cancer. Moringa oleifera (MO) exhibited various biological activities, including anticancer effects. Nevertheless, the effectiveness of their combination against pancreatic cancer has not yet been explored. This study evaluates the effect of MO and GEM against pancreatic cancer through network pharmacology. TCMSP, TCMID, and PubMed were used to identify and screen MO bioactive compounds. MO and GEM genes were predicted through DGIdb, CTD, and DrugBank. Pancreatic cancer genes were retrieved from OMIM and MalaCards. Protein–protein interaction (PPI) and compound-target-pathway network were established via STRING and Cytoscape. Gene ontology (GO) and pathway enrichment analysis were conducted using DAVID Bioinformatic Tools. Catechin, kaempferol, quercetin, and epicatechin that met the drug screening requirements, and three additional compounds, glucomoringin, glucoraphanin, and moringinine, were identified as bioactive compounds in MO. Catechin was found to be the main hub compound in MO. TP53, AKT1, VEGFA, and CCND1 from PPI network were discovered as hub genes to have biological importance in pancreatic cancer. GO and pathway analysis revealed that MO and GEM combination was mainly associated with cancer, including pancreatic cancer, through regulation of apoptosis. Combination therapy between MO and GEM might provide insight in pancreatic cancer treatment.

Highlights

According to the World Health Organization, cancer is defined as a disease that occurs in any organ or tissue of the body when the abnormal cells grow and divide uncontrollably beyond the usual boundaries and invade or spread to the other parts of the body or organs [1]
Only seven compounds were found to be listed in the TCMSP database, which are catechin, epicatechin, quercetin, kaempferol, caffeic acid, p-coumaric acid, and ferulic acid
Four compounds, which are catechin, epicatechin, quercetin, and kaempferol, were selected as the bioactive compound that met the requirement of the drug screening for further analyses (Table 1)

Summary

Introduction

According to the World Health Organization, cancer is defined as a disease that occurs in any organ or tissue of the body when the abnormal cells grow and divide uncontrollably beyond the usual boundaries and invade or spread to the other parts of the body or organs [1]. Gemcitabine (GEM), or known as 20 ,20 -difluorodeoxycytidine (dFdC), is a goldenstandard treatment for locally advanced and metastatic pancreatic cancer, since it was proven to be superior to fluorouracil (5-FU) in terms of overall survival, performance status, and pain control in 1997 [3,4]. It has been accepted widely, the chemoresistance is one of the major issues associated with this drug. The focus had been drawn towards traditional herbal medicine, which could be an alternative approach to overcome the limitation of gemcitabine against pancreatic cancer

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