Curcumin homing to the nucleolus: mechanism for initiation of an apoptotic program |
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| Institution: | 1. Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, China;2. Department of Anesthesiology, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong, Jiangsu Province 226001, China;3. Key Laboratory of Inflammation and Molecular Drug Target of Jiangsu Province, #19 Qixiu Road, Nantong 226001, China;1. Department of Chemical Biology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500 007, India;2. Division of Medicinal Chemistry & Pharmacology, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500 007, India;3. Functional Genomics and Gene Silencing Group, CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India;1. Centre for Biotechnology, Anna University, Chennai, Tamil Nadu 600025, India;2. Vector Control Research Centre, Indira Nagar, Puducherry 605006, India;1. Plant Ecology and Environmental Science Division, National Botanical Research Institute, Lucknow 226001, Uttar Pradesh, India;2. Academy of Scientific and Innovative Research (AcSIR), India;3. Department of Botany, Dolphin (PG) Institute, Manduwala, - Uttarakhand Technical University, Dehradun, Uttarakhand, India |
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| Abstract: | Curcumin is a plant-derived polyphenol that displays antitumor properties. Incubation of cultured SF-767 glioma cells with curcumin gave rise to intense intranuclear foci of curcumin fluorescence. In vitro studies revealed that nuclear homing by curcumin is not a result of DNA/chromatin binding. On the other hand, curcumin fluorescence colocalized with nucleophosmin, a nucleolus marker protein. To determine the temporal relationship between curcumin-induced apoptosis and nucleolar homing, confocal live cell imaging was performed. The data show that curcumin localization to the nucleolus occurs prior to cell surface exposure of phosphatidylserine. In studies of the mechanism of curcumin-induced apoptosis in SF-767 cells, its effect on the subcellular location of p14ARF was determined. Whereas p14ARF was confined to the nucleolus in untreated cells, 2 h following incubation with curcumin, it displayed a diffuse nuclear distribution. Given the role of nuclear p14ARF in binding the E3 ubiquitin ligase, mouse double minute 2 homolog (MDM2), the effect of curcumin treatment on cellular levels of the tumor suppressor protein, p53, was examined. Between 2 and 4 h following curcumin treatment, p53 levels increased with maximum levels reached by 8 h. Thus, curcumin homing to the nucleolus induces redistribution of p14ARF to the nucleoplasm where interaction with MDM2 leads to stabilization of p53, with subsequent initiation of apoptosis. |
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