Exploring inhibitory potential of Curcumin against various cancer targets by in silico virtual screening

Our plain-English summary of Exploring inhibitory potential of Curcumin against various cancer targets by in silico virtual screening, by A.B. Mahajanakatti, G. Murthy, N. Sharma, et al (Interdisciplinary Sciences, Computational Life Sciences, 2014).

The study

• Authors: A.B. Mahajanakatti, G. Murthy, N. Sharma, S. Skariyachan
• Journal: Interdisciplinary Sciences, Computational Life Sciences
• Published: 2014;6(1):13-24
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Various types of cancer accounts for 10% of total death worldwide which necessitates better therapeutic strategies. Curcumin, a curcuminoid present in Curcuma longa, shown to exhibit antioxidant, anti-inflammatory and anticarcinogenic properties. Present study, we aimed to analyze inhibitory properties of curcumin towards virulent proteins for various cancers by computer aided virtual screening. Based on literature studies, twenty two receptors were selected which have critical virulent functions in various cancer. The binding efficiencies of curcumin towards selected targets were studied by molecular docking. Out of all, curcumin showed best results towards epidermal growth factor (EGF), virulent protein of gastric cancer; glutathione-S-transferase Pi gene (GST-PI), virulent protein for prostate cancer; platelet-derived growth factor alpha (PDGFA), virulent protein for mesothelioma and glioma compared with their natural ligands. The calculated binding energies of their docked conformations with curcumin found to be -7.59 kcal/mol, -7.98 kcal/mol and -7.93 kcal/mol respectively. Further, a comparative study was performed to screen binding efficiency of curcumin with two conventional antitumor agents, litreol and triterpene. Docking studies revealed that calculated binding energies of docked complex of litreol and EGF, GST-PI and PDGFA were found to be -5.08 kcal/mol, -3.69 kcal/mol and -1.86 kcal/mol respectively. The calculated binding energies of triterpene with EGF and PDGFA were found to be -4.02 kcal/mol and -3.11 kcal/mol respectively, whereas GST-PI showed +6.07 kcal/mol, indicate poor binding. The predicted pharmacological features of curcumin found to be better than litreol and triterpene. Our study concluded that curcumin has better interacting properties towards these cancer targets than their normal ligands and conventional antitumor agents. Our data pave insight for designing of curcumin as novel inhibitors against various types of cancer.

In plain English

This computer-only (in silico) study tested no people, animals or cells, and did not study asbestos. The authors used docking software to predict how strongly curcumin, a turmeric compound, binds to 22 proteins they selected for roles in various cancers, several of which they linked to malignant pleural mesothelioma. More negative calculated binding energies meant stronger predicted binding. Curcumin's best values were −7.59 kcal/mol for epidermal growth factor (EGF, linked to gastric cancer), −7.98 for glutathione S-transferase Pi (GST-PI, prostate cancer) and −7.93 for platelet-derived growth factor alpha (PDGFA, malignant pleural mesothelioma and glioma). In the same calculations, imatinib gave −2.66 kcal/mol with PDGFA, and two plant compounds, litreol and triterpene, gave less negative values; triterpene gave +6.07 with GST-PI. The authors concluded that curcumin had better interacting properties than these compounds and the targets' normal ligands. They stated that their data were based on computer screening and that experimental studies are needed. Some numbers differ between sections of the article.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Computer-based (in silico) molecular docking and virtual screening study, with computer-predicted drug-likeness and toxicity
• Who was studied: No human or animal subjects. Twenty-two cancer-related protein targets were selected from cancer pathways in the KEGG database, using 3D structures retrieved from the PDB database. The authors' table links PDGFA, PDGFB, IGF1 and IGF1R to malignant pleural mesothelioma.
• Exposure: No asbestos exposure was studied. The compounds docked against the protein targets were curcumin and, for comparison, two plant-derived compounds, litreol and triterpene. Known inhibitors of three targets were also docked: gefitinib, celecoxib and lapatinib for EGF, buthionine sulfoximine for GST-PI, and imatinib for PDGFA.
• Main results:
  • Curcumin showed its best calculated binding energies with EGF (−7.59 kcal/mol), GST-PI (−7.98 kcal/mol) and PDGFA (−7.93 kcal/mol)
  • The authors described PDGFA as having a role in malignant pleural mesothelioma and glioma
  • In the authors' docking, imatinib bound PDGFA with a calculated binding energy of −2.66 kcal/mol, compared with −7.93 kcal/mol for curcumin
  • Litreol's calculated binding energies with EGF, GST-PI and PDGFA were −5.08, −3.69 and −1.86 kcal/mol respectively
  • Triterpene's calculated binding energies were −4.02 kcal/mol with EGF and −3.11 kcal/mol with PDGFA. With GST-PI it gave +6.07 kcal/mol, which the authors described as poor binding.
• The authors' conclusion: The authors concluded that curcumin has better interacting properties towards these cancer targets than their normal ligands and than the conventional antitumor agents tested
• Limitations the authors state:
  • The authors stated that the data come mainly from computer-aided virtual screening, and that further experimental studies are required to confirm them

Topics

Medical terms in this study, explained in our Lexicon: Stomach Cancer, Glutathione (GSH), Platelet-Derived Growth Factor (PDGF), Mesothelioma.

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