Targeting Mortalin by Embelin Causes Activation of Tumor Suppressor p53 and Deactivation of Metastatic Signaling in Human Breast Cancer Cells

• DOI: 10.1371/journal.pone.0138192
• Publication Date: 2015-09-16T20:07:10Z
• Authors: Nupur Nigam; Abhinav Grover; Sukriti Goyal; Shashank P. Katiyar; Priyanshu Bhargava; Pi-Chao Wang; Durai Sundar; Sunil C. Kaul; Renu Wadhwa
• Keywords: Science; Blotting, Western; Protein Array Analysis; Apoptosis; Breast Neoplasms; Real-Time Polymerase Chain Reaction; 03 medical and health sciences; Benzoquinones; Tumor Cells, Cultured; Humans; HSP70 Heat-Shock Proteins; RNA, Messenger; Neoplasm Metastasis; Cell Proliferation; Primulaceae; 0303 health sciences; Reverse Transcriptase Polymerase Chain Reaction; Q; R; 3. Good health; Gene Expression Regulation, Neoplastic; Medicine; Female; Tumor Suppressor Protein p53; Research Article; Signal Transduction

Embelin, a natural quinone found in the fruits of Embelia ribes, is commonly used Ayurvedic home medicine for variety therapeutic potentials including anti-inflammation, anti-fever, anti-bacteria and anti-cancer. Molecular mechanisms these activities cellular targets have not been clarified to-date. We demonstrate that embelin inhibits mortalin-p53 interactions, activates p53 protein tumor cells. provide bioinformatics, molecular docking experimental evidence to binding affinity with mortalin p53. Binding mortalin/p53 abrogates their complex resulted nuclear translocation transcriptional activation function causing growth arrest cancer Furthermore, analyses factors metastatic signaling using antibody membrane array revealed downregulation embelin-treated also causes attenuation several other proteins involved Based on dynamics data, it concluded anticancer activity involves targeting mortalin, inactivation signaling.