Plumbagin, isolated from Plumbago zeylanica, induces cell death through apoptosis in human pancreatic cancer cells.
ABSTRACT Pancreatic cancer is one of the most resistant malignancies. Several studies have indicated that plumbagin isolated from Plumbago zeylanica possesses anticancer activity. However, its antitumor effects against pancreatic cancer have not been explored.
We investigated the effect of plumbagin on the growth of human pancreatic carcinoma cells and its possible underlying mechanisms.
Plumbagin inhibited the growth of Panc-1 and Bxpc-3 cells in a dose-dependent and time-dependent manner. Liu's staining and transmission electron microscopy demonstrated morphological changes resembling apoptosis in Panc-1 cells treated with plumbagin. The degree of apoptosis was assessed by measuring the proportions of sub-G(1), annexin V+/propidium iodide-, and terminal- deoxynucleotidyl-transferase-mediated-nick-end labeling (TUNEL)+ cells, and a significant increment in apoptotic cells was observed. Exposure to plumbagin caused the upregulation of Bax, a rapid decline in mitochondrial transmembrane potential, apoptosis-inducing factor overexpression in cytosol, and the cleavage of procaspase-9 and poly ADP-ribose polymerase. Activation of caspase-3, but not caspase-8, was evidenced by fluorometric substrate assay. Pretreatment with caspase inhibitors did not block plumbagin-induced apoptosis. Alternatively, it is possible that plumbagin downregulated phosphoinositide 3-kinase activity through a negative feedback mechanism. In an orthotopic pancreatic tumor model, plumbagin markedly inhibited the growth of Panc-1 xenografts without any significant effect on leukocyte counts or body weight.
Plumbagin may induce apoptosis in human pancreatic cancer cells primarily through the mitochondria-related pathway followed by both caspase-dependent and caspase-independent cascades. It indicates that plumbagin can be potentially developed as a novel therapeutic agent against pancreatic cancer.
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ABSTRACT: Synthesis of compound libraries and their concurrent assessment as selective reagents for probing and modulating biological function continues to be an active area of chemical biology. Microwave-assisted solid-phase Dötz benzannulation reactions have been used to inexpensively synthesize 2, 3-disubstituted-1, 4-naphthoquinone derivatives. Herein, we report the biological testing of a small library of such compounds using a murine fibroblast cell line (L929). Assessment of cellular viability identified three categories of cytotoxic compounds: no toxicity, low/intermediate toxicity and high toxicity. Increased levels of Annexin-V-positive staining and of caspase 3 activity confirmed that low, intermediate, and highly toxic compounds promote cell death. The compounds varied in their ability to induce mitochondrial depolarization and formation of reactive oxygen species (ROS). Both cytotoxic and non-cytotoxic compounds triggered mitochondrial depolarization, while one highly cytotoxic compound did not. In addition, all cytotoxic compounds promoted increased intracellular ROS but the cells were only partially protected from compound-induced apoptosis when in the presence of superoxide dismutase, catalase, or ascorbic acid suggesting utilization of additional pro-death mechanisms. In summary, nine of twelve (75%) 1, 4-naphthoquinone synthetic compounds were cytotoxic. Although the mitochondria did not appear to be a central target for induction of cell death, all of the cytotoxic compounds induced ROS formation. Thus, the data demonstrate that the synthesis regime effectively created cytotoxic compounds highlighting the potential use of the regime and its products for the identification of biologically relevant reagents.PLoS ONE 09/2014; 9(9):e106828. DOI:10.1371/journal.pone.0106828 · 3.53 Impact Factor
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ABSTRACT: The present review aimed to compile up to date and comprehensive information of Plumbago zeylanica with special emphasis on its phytochemistry, various scientifically documented pharmacological activities, traditional and folk medicine uses. Traditional system of medicinal consists of large number of plants with various medicinal and pharmacological uses and hence represents a priceless tank of new bioactive molecules. P. zeylanica is one amongst these, found all over the world. In this review, we have attempted to highlight the work carried out on P. zeylanica. It is commonly known as 'Chitraka', and has been recognized in different traditional system of medicines for the treatment of various diseases of human beings in the form of paste and powder. Plant mainly contains naphthoquinones and steroidal compounds. Different parts of this plant are traditionally claimed to be used for the treatment of ailments including anti-fungal, anti-tumor, disease of heart, rheumatic pains, liver diseases, fever, diabetes, and kidney disease to list of few.African journal of pharmacy and pharmacology 12/2011; 5(25). DOI:10.5897/AJPP11.739 · 0.84 Impact Factor
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ABSTRACT: There is very limited information regarding plants used by traditional healers in Bandarban Hill Tracts (BHT), Bangladesh for treating general as well as complex ailments. Current study provides significant ethnopharmacological information, both qualitative and quantitative on medical plants in BHT.Journal of Ethnopharmacology 05/2014; DOI:10.1016/j.jep.2014.05.043 · 2.94 Impact Factor