Effects of Betulinic Acid Alone and in Combination with Irradiation in Human Melanoma Cells  Edgar Selzer, Emilio Pimentel, Volker Wacheck, Werner Schlegel,

Slides:



Advertisements
Similar presentations
The Combined Effects of Hematoporphyrin Monomethyl Ether-SDT and Doxorubicin on the Proliferation of QBC939 Cell Lines  Lei Liang, Sheng Xie, Lin Jiang,
Advertisements

Vemurafenib Induces Senescence Features in Melanoma Cells
Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor–κB and IκBα kinase in human multiple myeloma cells, leading to.
Volker Assmann, Christina Fieber, Peter Herrlich, Martin Hofmann 
Importance of Tissue Transglutaminase in Repair of Extracellular Matrices and Cell Death of Dermal Fibroblasts After Exposure to a Solarium Ultraviolet.
Testosterone promotes apoptotic damage in human renal tubular cells
Volume 120, Issue 2, Pages (January 2005)
Tumor Necrosis Factor α Increases and α-Melanocyte-Stimulating Hormone Reduces Uveal Melanoma Invasion Through Fibronectin  Irene Cantón, Paula C. Eves,
Efficient TRAIL-R1/DR4-Mediated Apoptosis in Melanoma Cells by Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)  Bahtier M. Kurbanov, Christoph.
Regulation of Human Melanoma Growth and Metastasis by AGE–AGE Receptor Interactions  Riichiro Abe, Tadamichi Shimizu, Hiroshi Sugawara, Hirokazu Watanabe,
The Bax/Bcl-2 Ratio Determines the Susceptibility of Human Melanoma Cells to CD95/Fas-Mediated Apoptosis  Monika Raisova, Amir M. Hossini, Jürgen Eberle,
Phosphatidylinositol 3-Kinase/Akt-Dependent and -Independent Protection Against Apoptosis in Normal Human Melanocytes  Masahiro Oka, Akiko Kageyama, Mizuho.
Valentina Manfé, Edyta Biskup, Peter Johansen, Maria R
17β-estradiol, Progesterone, and Dihydrotestosterone Suppress the Growth of Human Melanoma by Inhibiting Interleukin-8 Production  Naoko Kanda, Shinichi.
Protodynamic Intracellular Acidification by cis-Urocanic Acid Promotes Apoptosis of Melanoma Cells In Vitro and In Vivo  Jarmo K. Laihia, Janne P. Kallio,
All-trans Retinoic Acid Induces Differentiation and Apoptosis of Murine Melanocyte Precursors with Induction of the Microphthalmia-Associated Transcription.
Clusterin Regulates Drug-Resistance in Melanoma Cells
Decreased Growth Inhibitory Responses of Squamous Carcinoma Cells to Interferon-γ Involve Failure to Recruit cki Proteins into cdk2 Complexes  Beth L.
AT-101, a Pan-Bcl-2 Inhibitor, Leads to Radiosensitization of Non-small Cell Lung Cancer  Luigi Moretti, MD, Bo Li, MD, Kwang Woon Kim, PhD, Heidi Chen,
Hypertrophic Scar Cells Fail to Undergo a Form of Apoptosis Specific to Contractile Collagen—The Role of Tissue Transglutaminase  Claire Linge, Janette.
Terameprocol (Tetra-O-Methyl Nordihydroguaiaretic Acid), an Inhibitor of Sp1-Mediated Survivin Transcription, Induces Radiosensitization in Non-small.
Delphinidin, an Anthocyanidin in Pigmented Fruits and Vegetables, Protects Human HaCaT Keratinocytes and Mouse Skin Against UVB-Mediated Oxidative Stress.
Green Tea Polyphenols Prevent Ultraviolet Light-Induced Oxidative Damage and Matrix Metalloproteinases Expression in Mouse Skin  Praveen K. Vayalil, Anshu.
Marcel C. Pasch  Journal of Investigative Dermatology 
Selective Induction of Apoptosis in Melanoma Cells by Tyrosinase Promoter-Controlled CD95 Ligand Overexpression  Lothar F. Fecker, Christoph C. Geilen,
Einar K. Rofstad, Bjørn A. Graff  Journal of Investigative Dermatology 
Shalini S. Tibudan, Yihua Wang, Mitchell F. Denning 
Gangliosides GD1b, GT1b, and GQ1b Suppress the Growth of Human Melanoma by Inhibiting Interleukin-8 Production: the Inhibition of Adenylate Cyclase1 
Inhibition of CRM1-Mediated Nucleocytoplasmic Transport: Triggering Human Melanoma Cell Apoptosis by Perturbing Multiple Cellular Pathways  Gaurav Pathria,
Monika Jost, Csaba Kari, Ulrich Rodeck 
Bax Activation and Induction of Apoptosis in Human Keratinocytes by the Protein Kinase C δ Catalytic Domain  Leonid A. Sitailo, Shalini S. Tibudan, Mitchell.
The p53-Stabilizing Compound CP Enhances Ultraviolet-B-Induced Apoptosis in a Human Melanoma Cell Line MMRU  Yvonne Luu, Gang Li, Dr  Journal of.
Christiane Thallinger, Markus F
Death Receptor-Independent Apoptosis in Malignant Melanoma Induced by the Small- Molecule Immune Response Modifier Imiquimod  Michael P. Schön, B. Gregor.
PARP Determines the Mode of Cell Death in Skin Fibroblasts, but not Keratinocytes, Exposed to Sulfur Mustard  Dana Anderson, Betty Benton, Zhao-Qi Wang,
Volume 42, Issue 2, Pages (February 2005)
Hermine Schlagbauer-Wadl, Marieke Griffioen, Andrea van Elsas, Peter I
Rosiglitazone Inhibits Proliferation, Motility, and Matrix Metalloproteinase Production in Keratinocytes  Narasimharao Bhagavathula, Kamalakar C. Nerusu,
The Paracrine Role of Stem Cell Factor/c-kit Signaling in the Activation of Human Melanocytes in Ultraviolet-B-Induced Pigmentation  Akira Hachiya, Akemi.
Raymond L. Warters, Patrick J. Adamson, Christopher D. Pond, Sancy A
Oncogenic Ras-Induced Expression of Noxa and Beclin-1 Promotes Autophagic Cell Death and Limits Clonogenic Survival  Mohamed Elgendy, Clare Sheridan,
Different Susceptibility of Malignant versus Nonmalignant Human T Cells Toward Ultraviolet A-1 Radiation-Induced Apoptosis  Ritsuko Yamauchi, Akimichi.
The Cytotoxicity and Apoptosis Induced by 4-Tertiary Butylphenol in Human Melanocytes are Independent of Tyrosinase Activity  Fan Yang, Rangaprasad Sarangarajan,
FGF Expression Allows Nevus Cells to Survive in Three-Dimensional Collagen Gel Under Conditions that Induce Apoptosis in Normal Human Melanocytes  Tuomo.
Resistance of Human Melanoma Cells Against the Death Ligand TRAIL Is Reversed by Ultraviolet-B Radiation via Downregulation of FLIP  Elke Zeise, Michael.
Arsenic Induces Tumor Necrosis Factor α Release and Tumor Necrosis Factor Receptor 1 Signaling in T Helper Cell Apoptosis  Hsin-Su Yu, Gwo-Shing Chen 
Transforming Growth Factor β1 Induces Apoptosis in Normal Melanocytes but not in Nevus Cells Grown in Type I Collagen Gel  Tuomo Alanko  Journal of Investigative.
PPARδ Is a Type 1 IFN Target Gene and Inhibits Apoptosis in T Cells
Adenosine Receptors as Mediators of Both Cell Proliferation and Cell Death of Cultured Human Melanoma Cells  Stefania Merighi, Prisco Mirandola, Daniela.
Molecular Responses to Photogenotoxic Stress Induced by the Antibiotic Lomefloxacin in Human Skin Cells: From DNA Damage to Apoptosis  Laurent Marrot,
In Vitro and In Vivo Anti-Melanoma Effects of Ciglitazone
Green Tea Polyphenol Epigallocatechin-3-Gallate Suppresses Collagen Production and Proliferation in Keloid Fibroblasts via Inhibition of the STAT3-Signaling.
Bcl-2 Reduced and Fas Activated by the Inhibition of Stem Cell Factor/KIT Signaling in Murine Melanocyte Precursors  Satoko Kimura, Tamihiro Kawakami,
Activation of Dual Apoptotic Pathways in Human Melanocytes and Protection by Survivin  Tong Liu, Diana Biddle, Adrianne N. Hanks, Brook Brouha, Hui Yan,
Interferon-γ-Mediated Growth Regulation of Melanoma Cells: Involvement of STAT1- Dependent and STAT1-Independent Signals  Anja Bosserhoff  Journal of Investigative.
Tumor necrosis factor-α and lipopolysaccharide induce apoptotic cell death in bovine glomerular endothelial cells  Udo K. Meßmer, Verena A. Briner, Josef.
James Gailit, Mary J. Marchese, Richard R. Kew, Barry L. Gruber 
Differential Responses of S100A2 to Oxidative Stress and Increased Intracellular Calcium in Normal, Immortalized, and Malignant Human Keratinocytes  Tong.
A p38MAPK/HIF-1 Pathway Initiated by UVB Irradiation Is Required to Induce Noxa and Apoptosis of Human Keratinocytes  Kris Nys, An Van Laethem, Carine.
Decreased Phospholipase D (PLD) Activity in Ceramide-Induced Apoptosis of Human Keratinocyte Cell Line HaCaT  Yoshihiko Iwasaki-Bessho, Yoshiko Banno,
Formation of Antigenic Quinolone Photoadducts on Langerhans Cells Initiates Photoallergy to Systemically Administered Quinolone in Mice  Akihiro Ohshima,
The Herbal Medicine Sho-saiko-to Inhibits Growth and Metastasis of Malignant Melanoma Primarily Developed in ret-Transgenic Mice  Masashi Kato, Wei Liu,
Volume 3, Issue 5, Pages (May 2001)
Keratinocyte Apoptosis Induced by Ultraviolet B Radiation and CD95 Ligation – Differential Protection through Epidermal Growth Factor Receptor Activation.
CD40 Ligation Alters the Cell Cycle of Differentiating Keratinocytes
Relationship Between Cell-Associated Matrix Metalloproteinase 9 and Psoriatic Keratinocyte Growth  Nathalie Buisson-Legendre, Hervé Emonard, Philippe.
Pegylated and Conventional Interferon-α Induce Comparable Transcriptional Responses and Inhibition of Tumor Growth in a Human Melanoma SCID Mouse Xenotransplantation.
Bcl-2 and bcl-xL Antisense Oligonucleotides Induce Apoptosis in Melanoma Cells of Different Clinical Stages  Robert A. Olie, Christoph Hafner, Renzo Küttel,
Sphingosine-1-Phosphate and Its Potentially Paradoxical Effects on Critical Parameters of Cutaneous Wound Healing  Rüdiger Vogler, Bettina Sauer, Dong-Seok.
Matrix Metalloproteinase Inhibitor BB-3103 Unlike the Serine Proteinase Inhibitor Aprotinin Abrogates Epidermal Healing of Human Skin Wounds Ex Vivo1 
Presentation transcript:

Effects of Betulinic Acid Alone and in Combination with Irradiation in Human Melanoma Cells  Edgar Selzer, Emilio Pimentel, Volker Wacheck, Werner Schlegel, Hubert Pehamberger, Burkhard Jansen, Reinhard Kodym  Journal of Investigative Dermatology  Volume 114, Issue 5, Pages 935-940 (May 2000) DOI: 10.1046/j.1523-1747.2000.00972.x Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Effect of betulinic acid and radiotherapy on survival. (A) Survival of melanoma cell lines after treatment with betulinic acid alone or in combination with irradiation as assessed by inhibition of colony-forming ability. The survival curve of four melanoma cell lines (MES20, MES21, A375, and 518A2) is shown in the presence of betulinic acid alone (•) or in combination with γ irradiation (▪) at the indicated concentrations. Irradiation for all data points was a single dose of 2 Gy. Survival data are pooled and given as means together with the corresponding standard error of the mean. The colony-forming experiments were performed in triplicate for each cell line used. For details of colony-forming experiments, see Materials and Methods. (B) Graphical analysis of the combined effect of radiotherapy and betulinic acid on survival of melanoma cell lines. Open bars represent data obtained from survival experiments as measured by colony inhibition in the presence of the indicated concentrations of betulinic acid and after 2 Gy irradiation. The hatched bars represent the predicted (calculated) amount of growth inhibition if the effect was assumed to be purely additive. The survival experiments were performed as described under Materials and Methods. Data are given as means together with standard deviations. This analysis shows no synergy for the combined treatment. Journal of Investigative Dermatology 2000 114, 935-940DOI: (10.1046/j.1523-1747.2000.00972.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Influence of the timing of the exposure to betulinic acid on survival. This figure shows the results of addition of betulinic acid 8 h before irradiation (A), simultaneously (B), and 8 h after irradiation (C). Survival was measured by colony formation in three different melanoma cell lines. The concentration of betulinic acid used for the experiments was 2.5 μg per ml. Irradiation was performed with a dose of 2 Gy. The data presented are the results of three independent experiments (means and SEM) and are given in percentage survival (of the untreated control cells). Journal of Investigative Dermatology 2000 114, 935-940DOI: (10.1046/j.1523-1747.2000.00972.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Betulinic acid induces apoptosis in melanoma cells. AnnexinV-propidium iodide staining and fluorescence microscope visualization (×400) of melanoma cells (for a reference seeJansen et al. 1995) incubated for 24 h in the presence (A) or absence (B) of 10 μg betulinic acid per ml. In the control group (a) 7.1% (SD ±3.4%) of the cells stained positively (green staining) for Annexin V compared with 20.3% (SD ±4.7%) in the betulinic-acid-treated group (b). Scale bar: 50 μm. Journal of Investigative Dermatology 2000 114, 935-940DOI: (10.1046/j.1523-1747.2000.00972.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Growth analysis of human melanocytes and melanoma cell lines after treatment with betulinic acid reveals that normal melanocytes are less susceptible to inhibition by betulinic acid. For these experiments, three human melanocytic (neonatal) primary cell cultures and four different melanoma cell lines (MES20, MES21, A375, and 518A2) were used. In short, on the first day betulinic acid was added to the cell cultures (during the exponential growth phase) to the final concentrations indicated. Cell numbers were counted after 3 d. Data are given as means (plus standard deviations) of cell counts from the pooled data obtained from the experiments performed with normal melanocytes (•) and melanoma cell lines (▪). Journal of Investigative Dermatology 2000 114, 935-940DOI: (10.1046/j.1523-1747.2000.00972.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 DNA histograms of betulinic-acid-treated normal melanocytes and of a melanoma cell line. Melanoma cell line MES20 (lower panel) and normal melanocytes (upper panel) were treated with betulinic acid (5 μg per ml) for 8 h. After 8 h, cells were harvested and DNA histograms were determined as indicated in Materials and Methods. The melanoma cell line contains a significantly higher S-fraction than the normal melanocytes. Journal of Investigative Dermatology 2000 114, 935-940DOI: (10.1046/j.1523-1747.2000.00972.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Western blot analysis of Mcl-1 protein expression after treatment with betulinic acid – time course analysis in one cell line (Neo II-tr). The positions of the molecular weight markers (10 kDa protein ladder) and of Mcl-1 are indicated on the left. Betulinic acid was added to a final concentration of 5 μg per ml in the cell culture medium to cells in the exponential growth phase. Protein lysates were prepared and electrophoresis was carried out as described in Materials and Methods. After 4, 8, 24, and 48 h of cell culture the cells were analyzed for the expression of Mcl-1. As a loading control the Ponceau S stained membrane used for the Mcl-1 blot is shown in the figure below. A time course analysis with another transformed cell line (line Neo-IV-tr; the induction of Mcl-1 by betulinic acid after 24 h is shown in Figure 7c) showed nearly identical results (not shown). Journal of Investigative Dermatology 2000 114, 935-940DOI: (10.1046/j.1523-1747.2000.00972.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 7 Analysis of Bcl-2 family members and p53 protein expression in melanoma cell lines. Mcl-1 and p53 protein expression in controls (Ctrl), betulinic acid (BetA), and in irradiated (Rad) melanoma (MES20) cells. Mcl-1 and p53 protein expression after 18 h in two different melanoma cell lines (MES20 and 518A2) in the presence or absence of cisplatin (20 μM). Mcl-1, Bax, Bak, and Bad protein expression in two cell lines (Neo II-tr and Neo IV-tr) in the presence or absence of 5 μg betulinic acid per ml. Journal of Investigative Dermatology 2000 114, 935-940DOI: (10.1046/j.1523-1747.2000.00972.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions