Curcumin and Lung Cancer
Curcumin Inhibits Lung Cancer Cell Invasion and Metastasis through the
Tumor Suppressor
Huei-Wen Chen1, Jen-Yi Lee1, Ji-Ying Huang1, Chi-Chung Wang4, Wan-Jiun Chen1, Sheng-Fang Su1, Chia-Wen
Huang1, Chao-Chi Ho2, Jeremy J.W. Chen5, Meng-Feng Tsai6, Sung-Liang Yu3 and Pan-Chyr Yang2
1 Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, 2 Department of
Internal Medicine, National Taiwan University Hospital and National Taiwan University Medical College, and 3
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan
University, Taipei, Taiwan; 4 Graduate Institute of Basic Medicine, Fu Jen Catholic University, Taipei, Taiwan; and 5
Institute of Biomedical Science and Molecular Biology, College of Life Sciences, National Chung-Hsing University,
Taichung, Taiwan; and 6 Department of Molecular Biotechnology, Da-Yeh University, Changhua, Taiwan
Requests for reprints: Pan-Chyr Yang, Department of Internal Medicine, National Taiwan University Hospital and
National Taiwan University Medical College, No.7, Chung-Shan South Road, Taipei, 100, Taiwan. Phone: 886-2-
23562185; Fax: 886-2-23224793; E-mail: pcyang@ntu.edu.tw and Huei-Wen Chen, 155, Li-Nong Street, Taipei,
Taiwan. E-mail: hwchen@ym.edu.tw .
Curcumin (diferuloylmethane) is an active component of the spice turmeric and has a diversity of
antitumor activities. In this study, we found that curcumin can inhibit cancer cell invasion and
metastasis through activation of the tumor suppressor DnaJ-like heat shock protein 40 (HLJ1).
Human lung adenocarcinoma cells (CL1-5) treated with curcumin (1–20 µmol/L) showed a
concentration-dependent reduction in cell migration, invasion, and metastatic ability, and this was
associated with increased HLJ1 expression. Knockdown of HLJ1 expression by siRNA was able
to reverse the curcumin-induced anti-invasive and antimetastasis effects in vitro and in vivo. The
HLJ1 promoter and enhancer in a luciferase reporter assay revealed that curcumin
transcriptionally up-regulates HLJ1 expression through an activator protein (AP-1) site within the
HLJ1 enhancer. JunD, one of the AP-1 components, was significantly up-regulated by curcumin
(1–20 µmol/L) in a concentration- and time-dependent manner. Knockdown of JunD expression
could partially reduce the curcumin-induced HLJ1 activation and diminish the anti-invasive effect
of curcumin, indicating that JunD would seem to be involved in curcumin-induced HLJ1
expression. Curcumin was able to induce c-Jun NH2-kinase (JNK) phosphorylation, whereas the
JNK inhibitor (SP-600125) could attenuate curcumin-induced JunD and HLJ1 expression.
Activation of HLJ1 by curcumin further leads to up-regulation of E-cadherin and a suppression of
cancer cell invasion. Our results show that curcumin induces HLJ1, through activation of the
JNK/JunD pathway, and inhibits lung cancer cell invasion and metastasis by modulating E-
cadherin expression. This is a novel mechanism and supports the application of curcumin in anti–
cancer metastasis therapy. [Cancer Res 2008;68(18):7428–38]
Preventive role of curcumin in lung cancer
Maciej Balcerek, Irena Matławska
Katedra i Zakład Farmakognozji Collegium Medicum Uniwersytetu Mikołaja Kopernika w Bydgoszczy.
Carcinogens from cigarette smoke form the link between nicotine addiction and lung cancer, which is the leading
cause of cancer-related mortality in the world. One of the most frequently studied chemopreventive agents is a
curcumin, a natural compound extracted from turmeric that inhibits cell proliferation and induces apoptosis in human
leukaemia, prostate cancer, and non-small cell lung cancer. Curcumin (diferuoylmethane) is a major yellow pigment in
turmeric (Curcuma longa) and is widely used as a spice. Curcumin exhibits a variety of pharmacological effects, and
has been reported to have anti-inflammatory and anti-tumor activities.
Mesh-terms: Lung Neoplasms :: therapy; Curcumin :: therapeutic use; English Abstract; Humans; Phytotherapy ::
methods;
Tumor Suppressor
Huei-Wen Chen1, Jen-Yi Lee1, Ji-Ying Huang1, Chi-Chung Wang4, Wan-Jiun Chen1, Sheng-Fang Su1, Chia-Wen
Huang1, Chao-Chi Ho2, Jeremy J.W. Chen5, Meng-Feng Tsai6, Sung-Liang Yu3 and Pan-Chyr Yang2
1 Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, 2 Department of
Internal Medicine, National Taiwan University Hospital and National Taiwan University Medical College, and 3
Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan
University, Taipei, Taiwan; 4 Graduate Institute of Basic Medicine, Fu Jen Catholic University, Taipei, Taiwan; and 5
Institute of Biomedical Science and Molecular Biology, College of Life Sciences, National Chung-Hsing University,
Taichung, Taiwan; and 6 Department of Molecular Biotechnology, Da-Yeh University, Changhua, Taiwan
Requests for reprints: Pan-Chyr Yang, Department of Internal Medicine, National Taiwan University Hospital and
National Taiwan University Medical College, No.7, Chung-Shan South Road, Taipei, 100, Taiwan. Phone: 886-2-
23562185; Fax: 886-2-23224793; E-mail: pcyang@ntu.edu.tw and Huei-Wen Chen, 155, Li-Nong Street, Taipei,
Taiwan. E-mail: hwchen@ym.edu.tw .
Curcumin (diferuloylmethane) is an active component of the spice turmeric and has a diversity of
antitumor activities. In this study, we found that curcumin can inhibit cancer cell invasion and
metastasis through activation of the tumor suppressor DnaJ-like heat shock protein 40 (HLJ1).
Human lung adenocarcinoma cells (CL1-5) treated with curcumin (1–20 µmol/L) showed a
concentration-dependent reduction in cell migration, invasion, and metastatic ability, and this was
associated with increased HLJ1 expression. Knockdown of HLJ1 expression by siRNA was able
to reverse the curcumin-induced anti-invasive and antimetastasis effects in vitro and in vivo. The
HLJ1 promoter and enhancer in a luciferase reporter assay revealed that curcumin
transcriptionally up-regulates HLJ1 expression through an activator protein (AP-1) site within the
HLJ1 enhancer. JunD, one of the AP-1 components, was significantly up-regulated by curcumin
(1–20 µmol/L) in a concentration- and time-dependent manner. Knockdown of JunD expression
could partially reduce the curcumin-induced HLJ1 activation and diminish the anti-invasive effect
of curcumin, indicating that JunD would seem to be involved in curcumin-induced HLJ1
expression. Curcumin was able to induce c-Jun NH2-kinase (JNK) phosphorylation, whereas the
JNK inhibitor (SP-600125) could attenuate curcumin-induced JunD and HLJ1 expression.
Activation of HLJ1 by curcumin further leads to up-regulation of E-cadherin and a suppression of
cancer cell invasion. Our results show that curcumin induces HLJ1, through activation of the
JNK/JunD pathway, and inhibits lung cancer cell invasion and metastasis by modulating E-
cadherin expression. This is a novel mechanism and supports the application of curcumin in anti–
cancer metastasis therapy. [Cancer Res 2008;68(18):7428–38]
Preventive role of curcumin in lung cancer
Maciej Balcerek, Irena Matławska
Katedra i Zakład Farmakognozji Collegium Medicum Uniwersytetu Mikołaja Kopernika w Bydgoszczy.
Carcinogens from cigarette smoke form the link between nicotine addiction and lung cancer, which is the leading
cause of cancer-related mortality in the world. One of the most frequently studied chemopreventive agents is a
curcumin, a natural compound extracted from turmeric that inhibits cell proliferation and induces apoptosis in human
leukaemia, prostate cancer, and non-small cell lung cancer. Curcumin (diferuoylmethane) is a major yellow pigment in
turmeric (Curcuma longa) and is widely used as a spice. Curcumin exhibits a variety of pharmacological effects, and
has been reported to have anti-inflammatory and anti-tumor activities.
Mesh-terms: Lung Neoplasms :: therapy; Curcumin :: therapeutic use; English Abstract; Humans; Phytotherapy ::
methods;
Use Curcumin to Win the Fight!" |