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: Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment.Toxicology and Applied Pharmacology 04/2012; 262(1):80-90. DOI:10.1016/j.taap.2012.04.021
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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
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ABSTRACT: Alpha-glucosidase inhibitory activity of fifteen Indian medicinal plants has been evaluated by in vitro enzyme assay. Methanol extracts of Cyperus rotundus (tubers), Plumbago zeylanica (root), Symplocos racemosa (bark), and Terminalia arjuna (bark) had displayed 100% inhibition with the IC50 value of 3.98 μg/ml, 3.46 μg/ml, 8.16 μg/ml and 0.69 μg/ml, respectively. Bark extract of Terminalia arjuna is highly effective against alpha-glucosidase activity even at nanogram concentration. Plant parts of Piper retrofractum (stem), Zingiber officinale (rhizome), Acorus calamus (rhizome), Picrorhiza kurroa (rhizome), Marsdenia tenacissima (stem), Clerodendron serratum (root), and Rubia cordifolia (root) are not effective and they require high concentration to exhibit inhibition. Potential plants that show maximum inhibition at low concentration (<10 μg/ml) were subjected to kinetic analysis to determine the mode of inhibition of the enzyme. Cyperus rotundus, Symplocos racemosa and Terminalia arjuna exhibited uncompetitive inhibition and Plumbago zeylanica had displayed mixed inhibition to alpha-glucosidase enzyme activity. From the enzyme assay, we infer that Cyperus rotundus, Plumbago zeylanica, Symplocos racemosa and Terminalia arjuna contain potential alpha-glucosidase inhibitors that can be exploited for its use in the treatment of diabetes.International Journal of Pharmacy and Pharmaceutical Sciences 01/2011; Vol 3:267-274.