Presentation is loading. Please wait.

Presentation is loading. Please wait.

Droxinostat, a Histone Deacetylase Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cell Lines via Activation of the Mitochondrial Pathway and.

Published byPhilomena Lloyd Modified over 5 years ago

Similar presentations

Presentation on theme: "Droxinostat, a Histone Deacetylase Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cell Lines via Activation of the Mitochondrial Pathway and."— Presentation transcript:

1 Droxinostat, a Histone Deacetylase Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cell Lines via Activation of the Mitochondrial Pathway and Downregulation of FLIP  Jing Liu, Guangming Li, Xiang Wang, Liang Wang, Rui Zhao, Juanxia Wang, Yin Kong, Jie Ding, Juan Li, Lingyi Zhang  Translational Oncology  Volume 9, Issue 1, Pages (February 2016) DOI: /j.tranon Copyright © 2016 The Authors Terms and Conditions

2 Figure 1 Droxinostat inhibits cell proliferation and colony formation in HepG2 and SMMC-7721 cells. (A, D) MTT assay illustrating cell proliferation (0 to 120 hours) following treatment with various concentrations of droxinostat in HepG2 (A) and SMMC-7721 (D) cells. Data are expressed as absorbance values (490 nm), compared with untreated control cells. (B, E) The Real-time cell viability analysis ( RTCA RT-CES SP) system, another cell proliferation method, shown the following 96-hour treatment with various concentrations of droxinostat added at 24 hours in HepG2 (b) and SMMC-7721 (E) cells. Data are expressed as CI, compared with untreated control cells. (C, F) Number of colonies in HepG2 (C) and SMMC-7721 (F) cells after treatment with 20 μM droxinostat at 15 days. Results are expressed as number of colonies, compared with the control group (mean ± SE) (*P < .05, **P < .01). Translational Oncology 2016 9, 70-78DOI: ( /j.tranon ) Copyright © 2016 The Authors Terms and Conditions

3 Figure 2 Droxinostat suppresses HDAC3 expression and acetylates histones H3 and H4. HepG2 (A) and SMMC-7721(B) cells were cultured with 0, 10, 20, or 40 μM droxinostat for 48 hours. Western blot analysis using antibodies against HDAC3, Ac-H3, and Ac-H4 was performed after 48-hour incubation with droxinostat. Internal reference protein loading was verified via the detection of β-actin. (B, D, F, H) Protein expression, expressed as relative content, was examined using Gray analysis and compared with that in the control group (mean ± SE) (*P < .05, **P < .01). Translational Oncology 2016 9, 70-78DOI: ( /j.tranon ) Copyright © 2016 The Authors Terms and Conditions

4 Figure 3 Droxinostat induces HepG2 cell apoptosis by activating the mitochondrial apoptotic pathway and downregulating expression of FLIP. (A) Apoptotic cells were determined via flow cytometry following staining with Annexin V and PI. (B) Apoptosis rates of HepG2 cells treated with different concentrations of droxinostat were analyzed using bar graphs. (C) mRNA levels of genes related to the mitochondrial p53 apoptosis pathway were analyzed using qRT-PCR. (D) Levels of proteins associated with the mitochondrial p53 apoptosis pathway were analyzed via Western blot. (E) The relative contents of proteins of the mitochondrial p53 apoptosis pathway were analyzed using bar graphs. (F) Bax/Bcl-2 protein ratio. (G) Protein levels related to FLIP and caspase-8 were analyzed via Western blot. (H) Relative FLIP and caspase-8 levels were analyzed using bar graphs. Data are shown as means ± SE of three independent experiments, *P < .05, **P < .01, compared with untreated control cells (no droxinostat). Translational Oncology 2016 9, 70-78DOI: ( /j.tranon ) Copyright © 2016 The Authors Terms and Conditions

5 Figure 4 Droxinostat induces apoptosis in SMMC-7721 cells by activating the mitochondrial apoptotic pathway and downregulating FLIP. (A) Apoptotic cells were determined via flow cytometry following staining with Annexin V and PI. (B) Apoptosis rates of SMMC-7721 cells treated with different concentrations of droxinostat were analyzed using bar graphs. (C) mRNA levels of genes related to the mitochondrial p53 apoptosis pathway were analyzed using qRT- PCR. (D) Levels of proteins associated with the mitochondrial p53 apoptosis pathway were analyzed via Western blot. (E) Relative contents of proteins from the mitochondrial p53 apoptosis pathway were analyzed using bar graphs. (F) Bax /Bcl-2 protein ratio. (G) Protein levels of FLIP and caspase-8 were analyzed via Western blot. (H) Relative contents of FLIP and caspase-8 were analyzed using bar graphs. Data are presented as means ± SE of three independent experiments, *P < .05, **P < .001, compared with untreated control cells (no droxinostat). Translational Oncology 2016 9, 70-78DOI: ( /j.tranon ) Copyright © 2016 The Authors Terms and Conditions

6 Figure 5 Knockdown of HDAC3 induces hepatoma cell apoptosis and acetylation of histones H3 and H4. A: Data obtained with HepG2 cells. (A) Apoptotic populations of HepG2 HDAC3-silenced cells determined via flow cytometry. (B) Analysis of apoptosis rates using bar graphs. (C) HDAC3 protein is downregulated by siRNA against HDAC3 in HepG2 cells. (D, E) Expression of cleaved PARP and cleaved caspase 3 proteins is significantly increased upon knockdown of HDAC3 in HepG2 cells. (F, G) Expression of Ace-H3 and Ace-H4 proteins is significantly increased upon knockdown of HDAC3 in HepG2 cells. B: Data obtained with SMMC-7721 cells. (H) Apoptotic population of SMMC-7721 HDAC3-silenced cells determined via flow cytometry. (I) Analysis of apoptosis rates using bar graphs. (J) HDAC3 is downregulated by siRNA against HDAC3 in SMMC-7721 cells. (H, L) Expression of cleaved caspase 3 is significantly increased upon knockdown of HDAC3 in SMMC-7721 cells. (M, N) Expression of Ace-H3 and Ace-H4 proteins is significantly increased upon knockdown of HDAC3 in SMMC-7721 cells. Translational Oncology 2016 9, 70-78DOI: ( /j.tranon ) Copyright © 2016 The Authors Terms and Conditions

Download ppt "Droxinostat, a Histone Deacetylase Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cell Lines via Activation of the Mitochondrial Pathway and."

Similar presentations

Metformin prevents glucotoxicity by alleviating oxidative and ER stress–induced CD36 expression in pancreatic beta cells  Jun Sung Moon, Udayakumar Karunakaran,

Metformin prevents glucotoxicity by alleviating oxidative and ER stress–induced CD36 expression in pancreatic beta cells  Jun Sung Moon, Udayakumar Karunakaran,
Cell Physiol Biochem 2014;33: DOI: /

Cell Physiol Biochem 2014;33: DOI: /
Molecular Therapy - Nucleic Acids

Molecular Therapy - Nucleic Acids
J. -F. Zhang, P. -Q. Liu, G. -H. Chen, M. -Q. Lu, C. -J. Cai, Y

J. -F. Zhang, P. -Q. Liu, G. -H. Chen, M. -Q. Lu, C. -J. Cai, Y
A Novel Cinnamide YLT26 Induces Breast Cancer Cells Apoptosis via ROS-Mitochondrial Apoptotic Pathway in Vitro and Inhibits.

A Novel Cinnamide YLT26 Induces Breast Cancer Cells Apoptosis via ROS-Mitochondrial Apoptotic Pathway in Vitro and Inhibits.
Cantharidin Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing Autophagy and Inducing Apoptosis in Vitro and in.

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 Combined Effects of Hematoporphyrin Monomethyl Ether-SDT and Doxorubicin on the Proliferation of QBC939 Cell Lines  Lei Liang, Sheng Xie, Lin Jiang,
Saikosaponin-D Enhances Radiosensitivity of Hepatoma Cells under Hypoxic Conditions by Inhibiting Hypoxia-Inducible Factor-1α Cell Physiol Biochem 2014;33:37-51.

Saikosaponin-D Enhances Radiosensitivity of Hepatoma Cells under Hypoxic Conditions by Inhibiting Hypoxia-Inducible Factor-1α Cell Physiol Biochem 2014;33:37-51.
MicroRNA-101 Inhibits Growth, Proliferation and Migration and Induces Apoptosis of Breast Cancer Cells by Targeting Sex-Determining Region Y-Box 2 Cell.

MicroRNA-101 Inhibits Growth, Proliferation and Migration and Induces Apoptosis of Breast Cancer Cells by Targeting Sex-Determining Region Y-Box 2 Cell.
Hailong Zhang, Wei Zhang, Yong Zhou, Yuhua Jiang, Shupeng Li 

Hailong Zhang, Wei Zhang, Yong Zhou, Yuhua Jiang, Shupeng Li 
Elevated FOXC2 Expression Promotes Invasion of HCC Cell Lines and is Associated with Poor Prognosis in Hepatocellular Carcinoma Cell Physiol Biochem 2017;44:99–109.

Elevated FOXC2 Expression Promotes Invasion of HCC Cell Lines and is Associated with Poor Prognosis in Hepatocellular Carcinoma Cell Physiol Biochem 2017;44:99–109.
Upregulation of miR-142-3p Improves Drug Sensitivity of Acute Myelogenous Leukemia through Reducing P-Glycoprotein and Repressing Autophagy by Targeting.

Upregulation of miR-142-3p Improves Drug Sensitivity of Acute Myelogenous Leukemia through Reducing P-Glycoprotein and Repressing Autophagy by Targeting.
Dual Inhibition of PI3K/AKT and MEK/ERK Pathways Induces Synergistic Antitumor Effects in Diffuse Intrinsic Pontine Glioma Cells  Y. Linda Wu, Uday Bhanu.

Dual Inhibition of PI3K/AKT and MEK/ERK Pathways Induces Synergistic Antitumor Effects in Diffuse Intrinsic Pontine Glioma Cells  Y. Linda Wu, Uday Bhanu.
Long Noncoding RNA HOTAIR Controls Cell Cycle by Functioning as a Competing Endogenous RNA in Esophageal Squamous Cell Carcinoma  Kewei Ren, Yahua Li,

Long Noncoding RNA HOTAIR Controls Cell Cycle by Functioning as a Competing Endogenous RNA in Esophageal Squamous Cell Carcinoma  Kewei Ren, Yahua Li,
Integrin αvβ6 Promotes Lung Cancer Proliferation and Metastasis through Upregulation of IL-8–Mediated MAPK/ERK Signaling  Pengwei Yan, Huanfeng Zhu, Li.

Integrin αvβ6 Promotes Lung Cancer Proliferation and Metastasis through Upregulation of IL-8–Mediated MAPK/ERK Signaling  Pengwei Yan, Huanfeng Zhu, Li.
Antitumor Effect of AZD4547 in a Fibroblast Growth Factor Receptor 2–Amplified Gastric Cancer Patient–Derived Cell Model  Jiryeon Jang, Hee Kyung Kim,

Antitumor Effect of AZD4547 in a Fibroblast Growth Factor Receptor 2–Amplified Gastric Cancer Patient–Derived Cell Model  Jiryeon Jang, Hee Kyung Kim,
Volume 8, Issue 5, Pages (May 2017)

Volume 8, Issue 5, Pages (May 2017)
SIRT1 Regulates the Chemoresistance and Invasiveness of Ovarian Carcinoma Cells  David Hamisi Mvunta, Tsutomu Miyamoto, Ryoichi Asaka, Yasushi Yamada,

SIRT1 Regulates the Chemoresistance and Invasiveness of Ovarian Carcinoma Cells  David Hamisi Mvunta, Tsutomu Miyamoto, Ryoichi Asaka, Yasushi Yamada,
Induction of E-Cadherin in Lung Cancer and Interaction with Growth Suppression by Histone Deacetylase Inhibition  Masatoshi Kakihana, MD, Tatsuo Ohira,

Induction of E-Cadherin in Lung Cancer and Interaction with Growth Suppression by Histone Deacetylase Inhibition  Masatoshi Kakihana, MD, Tatsuo Ohira,
Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway.

Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway.

Similar presentations

Ads by Google