Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human.

Slides:



Advertisements
Similar presentations
Cell Physiol Biochem 2014;33: DOI: /
Advertisements

Inducible EGFR T790M-Mediated Gefitinib Resistance in Non-small Cell Lung Cancer Cells Does Not Modulate Sensitivity to PI103 Provoked Autophagy  Flavia.
Expression of LKB1 tumor suppressor in non–small cell lung cancer determines sensitivity to 2-deoxyglucose  Landon J. Inge, PhD, Keith D. Coon, PhD, Michael.
Cantharidin Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing Autophagy and Inducing Apoptosis in Vitro and in.
The Combined Effects of Hematoporphyrin Monomethyl Ether-SDT and Doxorubicin on the Proliferation of QBC939 Cell Lines  Lei Liang, Sheng Xie, Lin Jiang,
The Autophagy Inhibitor Chloroquine Overcomes the Innate Resistance of Wild-Type EGFR Non-Small-Cell Lung Cancer Cells to Erlotinib  Yiyu Zou, PhD, Yi-He.
Hailong Zhang, Wei Zhang, Yong Zhou, Yuhua Jiang, Shupeng Li 
Bovine lactoferricin B induces apoptosis of human gastric cancer cell line AGS by inhibition of autophagy at a late stage  W.-R. Pan, P.-W. Chen, Y.-L.
EZH2 Promotes E2F-Driven SCLC Tumorigenesis through Modulation of Apoptosis and Cell-Cycle Regulation  Roland Hubaux, PhD, Kelsie L. Thu, BSc, Bradley.
Juewon Kim, Hyunjung Choi, Eun-Gyung Cho, Tae R. Lee 
Shinichi Sakamoto, Steven Schwarze, Natasha Kyprianou  European Urology 
Shinichi Sakamoto, Steven Schwarze, Natasha Kyprianou  European Urology 
Upregulation of PD-L1 by EGFR Activation Mediates the Immune Escape in EGFR- Driven NSCLC: Implication for Optional Immune Targeted Therapy for NSCLC Patients.
Vemurafenib Induces Senescence Features in Melanoma Cells
by Pascal Gelebart, Mona Anand, Hanan Armanious, Anthea C
Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor–κB and IκBα kinase in human multiple myeloma cells, leading to.
Tocotrienols Induce Apoptosis and Autophagy in Rat Pancreatic Stellate Cells Through the Mitochondrial Death Pathway  Mariana Rickmann, Eva C. Vaquero,
Aurora Kinase A Is Upregulated in Cutaneous T-Cell Lymphoma and Represents a Potential Therapeutic Target  Daniel Humme, Ahmed Haider, Markus Möbs, Hiroshi.
Yongping Shao, Kaitlyn Le, Hanyin Cheng, Andrew E. Aplin 
Hyperphosphatemia induces protective autophagy in endothelial cells through the inhibition of Akt/mTOR signaling  Yu-Juei Hsu, MD, PhD, Shih-Che Hsu,
Bertrand Poussier, MD, Alfredo C
Angiogenic effects of stromal cell-derived factor-1 (SDF-1/CXCL12) variants in vitro and the in vivo expressions of CXCL12 variants and CXCR4 in human.
Keloid Fibroblasts Resist Ceramide-Induced Apoptosis by Overexpression of Insulin- Like Growth Factor I Receptor  Hiroshi Ishihara, Hiroshi Yoshimoto,
Expression of LKB1 tumor suppressor in non–small cell lung cancer determines sensitivity to 2-deoxyglucose  Landon J. Inge, PhD, Keith D. Coon, PhD, Michael.
RAF Inhibition Overcomes Resistance to TRAIL-Induced Apoptosis in Melanoma Cells  Anja Berger, Sandra-Annika Quast, Michael Plötz, Nicholas-Frederik Kuhn,
Hailong Zhang, Wei Zhang, Yong Zhou, Yuhua Jiang, Shupeng Li 
Volume 134, Issue 1, Pages (January 2008)
The Zinc Ionophore PCI-5002 Radiosensitizes Non-small Cell Lung Cancer Cells by Enhancing Autophagic Cell Death  Kwang Woon Kim, PhD, Christina K. Speirs,
Hyperphosphatemia induces protective autophagy in endothelial cells through the inhibition of Akt/mTOR signaling  Yu-Juei Hsu, MD, PhD, Shih-Che Hsu,
Volume 96, Issue 10, Pages (May 2009)
Enhancement of depsipeptide-mediated apoptosis of lung or esophageal cancer cells by flavopiridol: Activation of the mitochondria-dependent death-signaling.
The cell cycle and acute kidney injury
Dienogest enhances autophagy induction in endometriotic cells by impairing activation of AKT, ERK1/2, and mTOR  JongYeob Choi, Ph.D., MinWha Jo, M.S.,
Combined Radiotherapy and Anti–PD-L1 Antibody Synergistically Enhances Antitumor Effect in Non–Small Cell Lung Cancer  Xiaomei Gong, MD, PhD, Xuefei Li,
Volume 122, Issue 2, Pages (February 2002)
Ropivacaine- and bupivacaine-induced death of rabbit annulus fibrosus cells in vitro: involvement of the mitochondrial apoptotic pathway  X.-Y. Cai, Y.
Plakoglobin Deficiency Protects Keratinocytes from Apoptosis
Sensitization of Melanoma Cells for Death Ligand TRAIL Is Based on Cell Cycle Arrest, ROS Production, and Activation of Proapoptotic Bcl-2 Proteins  Sandra-Annika.
Inducible EGFR T790M-Mediated Gefitinib Resistance in Non-small Cell Lung Cancer Cells Does Not Modulate Sensitivity to PI103 Provoked Autophagy  Flavia.
Volume 136, Issue 4, Pages e3 (April 2009)
The Autophagy Inhibitor Chloroquine Overcomes the Innate Resistance of Wild-Type EGFR Non-Small-Cell Lung Cancer Cells to Erlotinib  Yiyu Zou, PhD, Yi-He.
Involvement of Oxidative Stress in Apoptosis Induced by a Mixture of Isothiazolinones in Normal Human Keratinocytes  Anna Ettorre, Paolo Neri, Anna Di.
Hypoxia Impairs Skin Myofibroblast Differentiation and Function
Inhibiting MDM2-p53 Interaction Suppresses Tumor Growth in Patient-Derived Non– Small Cell Lung Cancer Xenograft Models  Josephine Hai, PhD, Shingo Sakashita,
All-trans Retinoic Acid Induces Differentiation and Apoptosis of Murine Melanocyte Precursors with Induction of the Microphthalmia-Associated Transcription.
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,
The Human Immunodeficiency Virus Protease Inhibitor Ritonavir Inhibits Lung Cancer Cells, in Part, by Inhibition of Survivin  Anjaiah Srirangam, PhD,
Volume 22, Issue 3, Pages (March 2015)
Terameprocol (Tetra-O-Methyl Nordihydroguaiaretic Acid), an Inhibitor of Sp1-Mediated Survivin Transcription, Induces Radiosensitization in Non-small.
FcɛRI cross-linking and IL-3 protect human basophils from intrinsic apoptotic stress  Lionel Rohner, MSc, Ramona Reinhart, PhD, Björn Hagmann, PhD, Andrea.
BV6, an IAP Antagonist, Activates Apoptosis and Enhances Radiosensitization of Non- small Cell Lung Carcinoma In Vitro  Wenyan Li, MD, PhD, Bo Li, MD,
Brian Poligone, Elaine S. Gilmore, Carolina V
Volume 7, Issue 1, Pages (April 2014)
Inhibition of CRM1-Mediated Nucleocytoplasmic Transport: Triggering Human Melanoma Cell Apoptosis by Perturbing Multiple Cellular Pathways  Gaurav Pathria,
IL-6 Secreted from Cancer-Associated Fibroblasts Mediates Chemoresistance in NSCLC by Increasing Epithelial-Mesenchymal Transition Signaling  Yasushi.
Down-Regulation of SOX2 Underlies the Inhibitory Effects of the Triphenylmethane Gentian Violet on Melanoma Cell Self-Renewal and Survival  Silvia Pietrobono,
Bax Activation and Induction of Apoptosis in Human Keratinocytes by the Protein Kinase C δ Catalytic Domain  Leonid A. Sitailo, Shalini S. Tibudan, Mitchell.
Propionibacterium acnes Induces Autophagy in Keratinocytes: Involvement of Multiple Mechanisms  Klára Megyeri, László Orosz, Szilvia Bolla, Lilla Erdei,
Apoptosis Induction by SAHA in Cutaneous T-Cell Lymphoma Cells Is Related to Downregulation of c-FLIP and Enhanced TRAIL Signaling  Nadya Al-Yacoub, Lothar.
Molecular Therapy - Nucleic Acids
Role of NF-κB Activity in Apoptotic Response of Keratinocytes Mediated by Interferon-γ, Tumor Necrosis Factor-α, and Tumor-Necrosis-Factor-Related Apoptosis-Inducing.
Chadrick E. Denlinger, MD, Brian K. Rundall, DO, Michael D
Volume 19, Issue 1, Pages (April 2017)
Mark A. Rovedo, Nancy L. Krett, Steven T. Rosen 
Hydroxychloroquine Modulates Metabolic Activity and Proliferation and Induces Autophagic Cell Death of Human Dermal Fibroblasts  Bettina Ramser, Agatha.
Volume 41, Issue 5, Pages (November 2004)
Volume 19, Issue 1, Pages (April 2017)
Gold Nanoparticles for BCR-ABL1 Gene Silencing: Improving Tyrosine Kinase Inhibitor Efficacy in Chronic Myeloid Leukemia  Raquel Vinhas, Alexandra R.
Volume 3, Issue 5, Pages (May 2001)
Quercetin induces autophagy, blocks cell cycle and activation of ERK and JNK signaling pathways participates in the G1 arrest in P39 cells. Quercetin induces.
Presentation transcript:

Induction of Forkhead Class box O3a and apoptosis by a standardized ginsenoside formulation, KG-135, is potentiated by autophagy blockade in A549 human lung cancer cells  Chih-Jung Yao, Jyh-Ming Chow, Shuang-En Chuang, Chia-Lun Chang, Ming-De Yan, Hsin-Lun Lee, I-Chun Lai, Pei-Chun Lin, Gi-Ming Lai  Journal of Ginseng Research  Volume 41, Issue 3, Pages 247-256 (July 2017) DOI: 10.1016/j.jgr.2016.04.003 Copyright © 2016 Terms and Conditions

Fig. 1 Effects of KG-135 on the proliferation and cell cycle distribution of A549 human nonsmall cell lung cancer cells. (A) After treatment with KG-135 for 72 h, the cell viability of A549 cells was measured using sulforhodamine B binding assay. (B) The cell cycle distribution was analyzed using flow cytometry. Cell viability data are expressed as mean ± standard error and analyzed as described in Section 2. Journal of Ginseng Research 2017 41, 247-256DOI: (10.1016/j.jgr.2016.04.003) Copyright © 2016 Terms and Conditions

Fig. 2 Effects of KG-135 and autophagy inhibitor hydroxychloroquine (HCQ) on the cell viability of normal human fetal lung fibroblast WI-38 cells. (A) After treatment with KG-135 alone or in the presence of HCQ for 72 h, the cell viability was determined using sulforhodamine B binding assay and (B) examined using phase contrast microscopy, scale bar = 100 μm. Cell viability data are expressed as mean ± standard error and analyzed as described in Section 2. Journal of Ginseng Research 2017 41, 247-256DOI: (10.1016/j.jgr.2016.04.003) Copyright © 2016 Terms and Conditions

Fig. 3 Effects of KG-135 on the cell cycle regulation proteins and tumor suppressor FOXO3a of A549 human nonsmall cell lung cancer cells. (A) After treatment with KG-135 for 72 h, Western blot was used to analyze the protein levels of cyclin-dependent kinase (CDK)4, CDK6, cyclin D1, Rb, and pRb, (B) p18 and p27, and (C) FOXO3a. FOXO3a, Forkhead Class box O3a; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; pRb, phospho-retinoblastoma protein. Journal of Ginseng Research 2017 41, 247-256DOI: (10.1016/j.jgr.2016.04.003) Copyright © 2016 Terms and Conditions

Fig. 4 Effects of KG-135 and metformin on autophagy related proteins in A549 human nonsmall cell lung cancer cells. (A) After treatment with KG-135 or (B) metformin for 72 h, Western blot was used to analyze the protein levels of LC3-I, LC3-II, Beclin-1, and p62 (sequestosome 1). GAPDH, glyceraldehyde 3-phosphate dehydrogenase. Journal of Ginseng Research 2017 41, 247-256DOI: (10.1016/j.jgr.2016.04.003) Copyright © 2016 Terms and Conditions

Fig. 5 Effects of autophagy inhibitor hydroxychloroquine (HCQ) on KG-135-induced LC3-II accumulation and acidic vesicular organelle (AVO) formation in A549 human nonsmall cell lung cancer cells. (A) After treatment with KG-135 alone or in the presence of HCQ for 72 h, the protein levels of LC3-I and LC3-II were analyzed by Western blot. (B) As described in Section 2, the formation of acridine orange-stained AVOs was examined using fluorescence microscopy, scale bar = 50 μm and (C) quantified using flow cytometry. The AVOs in KG-135-treated cells showed bright red, whereas the cytoplasm and the nucleus showed dominant green fluorescence. The percentage of cells with bright red fluorescence (the upper two FL3-positive quadrants) is indicated in the parentheses of each flow cytometric dot plot. GAPDH, glyceraldehyde 3-phosphate dehydrogenase. Journal of Ginseng Research 2017 41, 247-256DOI: (10.1016/j.jgr.2016.04.003) Copyright © 2016 Terms and Conditions

Fig. 6 Effects of autophagy inhibitor hydroxychloroquine (HCQ) on KG-135-mediated growth inhibition and apoptosis induction in A549 human nonsmall cell lung cancer cells. (A) After treatment with KG-135 alone or in the presence of HCQ for 72 h, the cell viability was determined using sulforhodamine B binding assay and (B) examined using phase contrast microscopy, scale bar = 100 μm. (C) The sub-G1 apoptotic fraction was analyzed using flow cytometry. Journal of Ginseng Research 2017 41, 247-256DOI: (10.1016/j.jgr.2016.04.003) Copyright © 2016 Terms and Conditions

Fig. 7 Effects of autophagy inhibitor hydroxychloroquine (HCQ) on KG-135-mediated activation of apoptosis pathways and upregulation of tumor suppressor FOXO3a in A549 human nonsmall cell lung cancer cells. (A) The protein level of FOXO3a was analyzed using Western blot after treatment with KG-135 alone or in the presence of HCQ for 24 h and 72 h. (B) The extrinsic apoptosis-related proteins Fas ligand (FasL) and full-length caspase-8 were analyzed using Western blot after treatment with KG-135 alone or in the presence of HCQ for 48 h. (C) The mitochondrial (intrinsic) apoptosis-related proteins were analyzed using Western blot 48 h (survivin and caspase-9 cleaved at Asp315 and Asp330) and 72 h (Bcl-2) after treatment with KG-135 alone or in the presence of HCQ. FOXO3a, Forkhead Class box O3a; GAPDH, glyceraldehyde 3-phosphate dehydrogenase. Journal of Ginseng Research 2017 41, 247-256DOI: (10.1016/j.jgr.2016.04.003) Copyright © 2016 Terms and Conditions

Fig. S1 Effect of autophagy inhibitor hydroxychloroquine (HCQ) 25μM combined with 50 μg/mL of KG-135 on apoptosis induction in A549 human nonsmall cell lung cancer cells. After treatment with KG-135 (50 μg/mL) alone or in the presence of HCQ (25μM) for 72 h, the sub-G1 apoptotic fraction was analyzed with flow cytometry. Journal of Ginseng Research 2017 41, 247-256DOI: (10.1016/j.jgr.2016.04.003) Copyright © 2016 Terms and Conditions

Fig. S2 The FOXO3a protein in A549 cells decreases with the culture time. The protein level of FOXO3a was analyzed using Western blot after treatment with KG-135 for 4 h, 24 h, and 72 h. FOXO3a, Forkhead Class box O3a; GAPDH, glyceraldehyde 3-phosphate dehydrogenase. Journal of Ginseng Research 2017 41, 247-256DOI: (10.1016/j.jgr.2016.04.003) Copyright © 2016 Terms and Conditions

Fig. S3 Effects of KG-135 in H460 human large-cell lung cancer cells. (A) After treatment with KG-135 for 72 h, Western blot was used to analyze the protein levels of LC3-I, LC3-II, Beclin-1, and p62. (B) The protein level of FOXO3a and (C) sub-G1 apoptotic fraction were analyzed after treatment with KG-135 alone or in the presence of hydroxychloroquine (HCQ) for 72 h. H460 cells were maintained and treated with drugs in the same condition as that for A549 cells. FOXO3a, Forkhead Class box O3a; GAPDH, glyceraldehyde 3-phosphate dehydrogenase. Journal of Ginseng Research 2017 41, 247-256DOI: (10.1016/j.jgr.2016.04.003) Copyright © 2016 Terms and Conditions