Matrix metalloproteinase-9 (MMP9) has an essential role in cervical cancer metastasis. Sappan wood extract (SWE) from Caesalpinia sappan contains metabolites that have pharmacological effects and can potentially inhibit metastasis by targeting the protein markers. This research aims to discover the potency of compounds in C. sappan as chemopreventive agents for metastasis in cervical cancer by targeting MMP9. SWE was obtained by maceration with methanol and analyzed using thin layer chromatography (TLC). In vitro cytotoxicity test of SWE on HeLa cells was performed by direct counting method. MMP9 expression profiles and survival rates in cervical cancer patients were explored through bioinformatics studies by the GEPIA database. The CMAUP and PubChem databases were used to obtain the metabolomic profile of SWE. SWE compounds’ activities on target proteins were obtained through KNIME software, while its interaction with MMP9 was analyzed using molecular docking with MOE software. We obtained SWE with a yield of 9.7% w/w. The extract contains brazilin and is indicated by the spot appearance at Rf 0.375. The cytotoxicity of SWE against HeLa cells was considered potential as the IC50 value was 54.93 μg/mL. Based on the bioinformatics analysis, there is a significant difference in MMP9 expression between normal and cervical cancer tissue. The patient’s survival probability decreased if MMP9 was overexpressed. The molecular docking results showed that active compounds of SWE bind to the MMP9 inhibition site with higher affinity compared to the native ligand. This study reveals that SWE potential to be developed as a chemopreventive agent through metastasis inhibition in cervical cancer by targeting MMP9.Keywords: Caesalpinia sappan L., metastasis, bioinformatics, molecular docking, MOE.
Jatropha (Jatropha curcas) is often used as biodiesel because of the oil content in its seeds. The production of jatropha oil generates a byproduct in the form of jatropha seed meal, which contains compounds with cytotoxic activity and phorbol esters, as co-carcinogens and tumor promoters. Meanwhile, metastasis is one of the characteristics of cancer where the cells spread to another tissue. This study aimed to determine the potential of jatropha seed meal as a chemoprevention agent, particularly an antimetastatic one, under bioinformatic study and molecular docking. Genecards and DAVID were performed to explore the protein involved in the metastatic process and its gene ontology. The prediction target protein was caught by SwissTargetPrediction. Jatropha seed meal showed the presence of isoamericanol A, myricetin, daidzein, gallic acid, and rutin. There are 11 prediction target proteins correlated to metastatic in extracellular matrix components. Then we were docked to a protein involved in metastasis, matrix metalloproteinase (MMP)-9 (PDB ID: 6ESM) using MOE software. The docking score determined the interaction properties. The docking analysis revealed that isoamericanol A, daidzein, and myricetin exhibited better binding affinity than native ligands and other compounds. Moreover, based on our literature study, the jatropha seed meal contains isoamericanol A, rutin, myricetin, daidzein, and gallic acid, which present anticancer properties by inhibition of cell invasion and migration, cell cycle arrest induction, and suppression of the MMP-9 activity. Overall, jatropha seed meal has potential as an antimetastatic agent. A comprehensive study is needed to explore the possibility of developing it as a supportive agent in combination with a chemotherapeutic agent.
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