Extracts of Lycoris aurea Induce Apoptosis in Murine Sarcoma S180 Cells

Lycoris species have been known since long ago as a multi-utility ethnomedicinal herbal in China. It has been reported to exhibit a number of properties such as anticancer, neuroprotective, and antibacterial activities. In the present study, the anticancer efficacy of dichloromethane extracts of Lycoris aurea (DELA), was evaluated both in vivo and in vitro using murine sarcoma 180 cells. To evaluate the effects of DELA on apoptotic cell death, flow cytometry and Western blotting were performed. DELA demonstrated promising inhibition effects on sarcoma 180 cells in vitro and a 53.49% inhibitory rate on cancer cells in vivo. DELA treatment increased thymus indices and spleen indices in vivo, indicating that it reduced tumours, but did not damage the main immune organs. The DELA-evoked increase in apoptotic cell death was accompanied by occurrence of cleaved caspase-3 and decreases in the ratio of Bcl-2/Bax. Further purification and LCMS analysis showed DELA contained homolycorine, 2α-hydroxyoduline, oduline, hippeastrine, 2α-hydroxy-6-O- methyloduline, and 2α-methoxy-6-O-methyloduline. These results indicate that DELA exerted its anticancer effects, at least in part, by inducing cancer cell apoptosis and thus can be considered as a potential candidate agent for treatment of cancer.

[1]  Jing Liu,et al.  Apoptosis induced by lycorine in KM3 cells is associated with the G0/G1 cell cycle arrest. , 2007, Oncology reports.

[2]  Q. Qi,et al.  Breviscapine‐induced apoptosis of human hepatocellular carcinoma cell line HepG2 was involved in its antitumor activity , 2010, Phytotherapy research : PTR.

[3]  Y. Zu,et al.  SFE-CO2 Extract from Typhonium giganteum Engl. Tubers, Induces Apoptosis in Human Hepatoma SMMC-7721 Cells Involvement of a ROS-Mediated Mitochondrial Pathway , 2011, Molecules.

[4]  J C Reed,et al.  Antisense-mediated inhibition of BCL2 protooncogene expression and leukemic cell growth and survival: comparisons of phosphodiester and phosphorothioate oligodeoxynucleotides. , 1990, Cancer research.

[5]  S. Van slambrouck,et al.  Biological Evaluation of Structurally Diverse Amaryllidaceae Alkaloids and their Synthetic Derivatives: Discovery of Novel Leads for Anticancer Drug Design , 2009, Planta medica.

[6]  R. Kiss,et al.  The Amaryllidaceae isocarbostyril narciclasine induces apoptosis by activation of the death receptor and/or mitochondrial pathways in cancer cells but not in normal fibroblasts. , 2007, Neoplasia.

[7]  G. Ceriotti Narciclasine: an Antimitotic Substance from Narcissus Bulbs , 1967, Nature.

[8]  D. Waxman,et al.  Cyclophosphamide induces caspase 9-dependent apoptosis in 9L tumor cells. , 2001, Molecular pharmacology.

[9]  Yong Yang,et al.  The anticancer activities of wogonin in murine sarcoma S180 both in vitro and in vivo. , 2006, Biological & pharmaceutical bulletin.

[10]  G. Cragg,et al.  Antineoplastic agents, 105. Zephyranthes grandiflora. , 1984, Journal of natural products.

[11]  G. Chamorro-Cevallos,et al.  Chemoprotective effect of Spirulina (Arthrospira) against cyclophosphamide-induced mutagenicity in mice. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[12]  Qing Zhao,et al.  LYG-202, a new flavonoid with a piperazine substitution, shows antitumor effects in vivo and in vitro. , 2009, Biochemical and biophysical research communications.

[13]  J. W. Cook,et al.  Chapter XI Alkaloids of the Amaryllidaceae , 1952 .

[14]  J L Hartwell,et al.  Plants used against cancer. A survey. , 1970, Lloydia.

[15]  S. Manna,et al.  Epigallocatechin gallate induced apoptosis in Sarcoma180 cells in vivo: Mediated by p53 pathway and inhibition in U1B, U4-U6 UsnRNAs expression , 2006, Apoptosis.

[16]  R. Kiss,et al.  Amaryllidaceae alkaloids belonging to different structural subgroups display activity against apoptosis-resistant cancer cells. , 2010, Journal of natural products.

[17]  X. Jiao,et al.  Lycorine induces apoptosis and down-regulation of Mcl-1 in human leukemia cells. , 2009, Cancer letters.

[18]  M. Yamazaki,et al.  The inhibitory effect of lycorine on tumor cell apoptosis induced by polymorphonuclear leukocyte-derived calprotectin. , 1998, Immunopharmacology.

[19]  C. Codina,et al.  Cytotoxic activity of Amaryllidaceae alkaloids. , 1995, Planta medica.

[20]  R. Bauer,et al.  A petrol ether extract of the roots of Onosma paniculatum induces cell death in a caspase dependent manner. , 2010, Journal of ethnopharmacology.

[21]  D. H. Smith,et al.  Mass spectra of Amaryllidaceae alkaloids - The lycorenine series. , 1968 .

[22]  Mao Ye,et al.  Effects of lycorine on HL‐60 cells via arresting cell cycle and inducing apoptosis , 2004, FEBS letters.

[23]  Cody J. Champion,et al.  Bulbispermine: A Crinine‐Type Amaryllidaceae Alkaloid Exhibiting Cytostatic Activity toward Apoptosis‐Resistant Glioma Cells , 2012, ChemMedChem.

[24]  C. Pirker,et al.  Targeting of eEF1A with Amaryllidaceae isocarbostyrils as a strategy to combat melanomas , 2010, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[25]  Lantong Zhang,et al.  Comparative anticancer and antioxidant activities of different ingredients of Ginkgo biloba extract (EGb 761). , 2009, Planta medica.

[26]  T. Toube,et al.  357. The alkaloids of the amaryllidaceae. Part XII. The aromatic oxygenation patterns and stereochemistry of some trioxyaryl alkaloids of the hemiacetal and lactone series , 1965 .

[27]  P. Jeffs,et al.  Alkaloids of the Amaryllidaceae. 27. Structures of 9-O-demethylhomolycorine and 5.alpha.-hydroxyhomolycorine. Alkaloids of Crinum defixum, C. scabrum, and C. latifolium. Assignment of aromatic substitution patterns from 1H-coupled carbon-13 spectra , 1985 .

[28]  Ning Li,et al.  Immunomodulation and antitumor activity of kappa-carrageenan oligosaccharides. , 2006, Cancer letters.

[29]  C. Codina,et al.  Phytochemical differentiation of Galanthus nivalis and Galanthus elwesii (Amaryllidaceae): A case study , 2008 .

[30]  C. Codina,et al.  ALKALOIDS FROM NARCISSUS CV. SALOME , 1996 .

[31]  L. Szlávik,et al.  Alkaloids from Leucojum vernum and antiretroviral activity of Amaryllidaceae alkaloids. , 2004, Planta medica.

[32]  J. Buolamwini Novel anticancer drug discovery. , 1999, Current opinion in chemical biology.

[33]  J M Pezzuto,et al.  Cytotoxicity of Hymenocallis expansa alkaloids. , 1993, Journal of natural products.

[34]  C. Codina,et al.  Selective apoptosis-inducing activity of crinum-type Amaryllidaceae alkaloids. , 2007, Phytochemistry.

[35]  Luis Carrasco,et al.  Narciclasine: an antitumour alkaloid which blocks peptide bond formation by eukaryotic ribosomes , 1975, FEBS letters.

[36]  L. Witte,et al.  Capillary gas chromatography-mass spectrometry of Amaryllidaceae alkaloids , 1995 .

[37]  Jing Liu,et al.  Apoptosis of HL-60 cells induced by extracts from Narcissus tazetta var. chinensis. , 2006, Cancer letters.

[38]  Xueying Sun,et al.  Role of the spleen in cyclophosphamide-induced hematosuppression and extramedullary hematopoiesis in mice. , 2009, Archives of medical research.

[39]  J. McNulty,et al.  Pancratistatin causes early activation of caspase-3 and the flipping of phosphatidyl serine followed by rapid apoptosis specifically in human lymphoma cells , 2005, Cancer Chemotherapy and Pharmacology.

[40]  Nguyen Thi Ngoc Tram,et al.  Crinum L. (Amaryllidaceae). , 2002, Fitoterapia.

[41]  M. Cesta Normal Structure, Function, and Histology of the Spleen , 2006, Toxicologic pathology.

[42]  A. Porter,et al.  Emerging roles of caspase-3 in apoptosis , 1999, Cell Death and Differentiation.

[43]  A. Kornienko,et al.  Anticancer evaluation of structurally diverse Amaryllidaceae alkaloids and their synthetic derivatives , 2009, Phytochemistry Reviews.

[44]  J L Hartwell,et al.  PLANTS USED AGAINST CANCER , 1989 .

[45]  Yanjie Lu,et al.  MicroRNAs and apoptosis: implications in the molecular therapy of human disease , 2009, Clinical and experimental pharmacology & physiology.

[46]  Ning Li,et al.  Immunomodulation and antitumor activity of κ-carrageenan oligosaccharides , 2006 .