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Thymoquinone Inhibits Tumor Growth and Induces Apoptosis in a Breast Cancer Xenograft Mouse Model: The Role of p38 MAPK and ROS
by
Kumar, Alan Prem
, Woo, Chern Chiuh
, Hsu, Annie
, Sethi, Gautam
, Tan, Kwong Huat Benny
in
Acetylcysteine - pharmacology
/ Animal tissues
/ Animals
/ Annexin V
/ Antibiotics
/ Anticancer properties
/ Antineoplastic Agents - pharmacology
/ Antioxidants - metabolism
/ Antitumor activity
/ Apoptosis
/ Apoptosis - drug effects
/ Bcl-2 protein
/ Bcl-x protein
/ Benzoquinones - pharmacology
/ Breast cancer
/ Breast carcinoma
/ Breast Neoplasms - enzymology
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Cancer
/ Care and treatment
/ Catalase
/ Cell cycle
/ Cell growth
/ Cell Line, Tumor
/ Cell Proliferation - drug effects
/ Chemical compounds
/ Development and progression
/ Doxorubicin
/ Female
/ Gene expression
/ Gene Silencing
/ Genetic aspects
/ Glutathione
/ Growth
/ Health aspects
/ Histology
/ Humans
/ Imidazoles - pharmacology
/ Immunoglobulins
/ Immunohistochemistry
/ In vivo methods and tests
/ Iodides
/ Kinases
/ Liver
/ Liver - drug effects
/ Liver - enzymology
/ MAP kinase
/ Medicine
/ Mice
/ Molecular chains
/ Oxidative stress
/ Oxidizing agents
/ p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors
/ p38 Mitogen-Activated Protein Kinases - deficiency
/ p38 Mitogen-Activated Protein Kinases - genetics
/ p38 Mitogen-Activated Protein Kinases - metabolism
/ Pharmacology
/ Phosphorylation
/ Phosphorylation - drug effects
/ Physiological aspects
/ Propidium iodide
/ Prostate
/ Proteins
/ Pyridines - pharmacology
/ Reactive Oxygen Species - metabolism
/ Staining
/ Superoxide dismutase
/ Superoxides
/ Survivin
/ Tissues
/ Tumorigenesis
/ Tumors
/ Xenograft Model Antitumor Assays
/ Xenografts
/ Xenotransplantation
/ XIAP protein
2013
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Thymoquinone Inhibits Tumor Growth and Induces Apoptosis in a Breast Cancer Xenograft Mouse Model: The Role of p38 MAPK and ROS
by
Kumar, Alan Prem
, Woo, Chern Chiuh
, Hsu, Annie
, Sethi, Gautam
, Tan, Kwong Huat Benny
in
Acetylcysteine - pharmacology
/ Animal tissues
/ Animals
/ Annexin V
/ Antibiotics
/ Anticancer properties
/ Antineoplastic Agents - pharmacology
/ Antioxidants - metabolism
/ Antitumor activity
/ Apoptosis
/ Apoptosis - drug effects
/ Bcl-2 protein
/ Bcl-x protein
/ Benzoquinones - pharmacology
/ Breast cancer
/ Breast carcinoma
/ Breast Neoplasms - enzymology
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Cancer
/ Care and treatment
/ Catalase
/ Cell cycle
/ Cell growth
/ Cell Line, Tumor
/ Cell Proliferation - drug effects
/ Chemical compounds
/ Development and progression
/ Doxorubicin
/ Female
/ Gene expression
/ Gene Silencing
/ Genetic aspects
/ Glutathione
/ Growth
/ Health aspects
/ Histology
/ Humans
/ Imidazoles - pharmacology
/ Immunoglobulins
/ Immunohistochemistry
/ In vivo methods and tests
/ Iodides
/ Kinases
/ Liver
/ Liver - drug effects
/ Liver - enzymology
/ MAP kinase
/ Medicine
/ Mice
/ Molecular chains
/ Oxidative stress
/ Oxidizing agents
/ p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors
/ p38 Mitogen-Activated Protein Kinases - deficiency
/ p38 Mitogen-Activated Protein Kinases - genetics
/ p38 Mitogen-Activated Protein Kinases - metabolism
/ Pharmacology
/ Phosphorylation
/ Phosphorylation - drug effects
/ Physiological aspects
/ Propidium iodide
/ Prostate
/ Proteins
/ Pyridines - pharmacology
/ Reactive Oxygen Species - metabolism
/ Staining
/ Superoxide dismutase
/ Superoxides
/ Survivin
/ Tissues
/ Tumorigenesis
/ Tumors
/ Xenograft Model Antitumor Assays
/ Xenografts
/ Xenotransplantation
/ XIAP protein
2013
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Thymoquinone Inhibits Tumor Growth and Induces Apoptosis in a Breast Cancer Xenograft Mouse Model: The Role of p38 MAPK and ROS
by
Kumar, Alan Prem
, Woo, Chern Chiuh
, Hsu, Annie
, Sethi, Gautam
, Tan, Kwong Huat Benny
in
Acetylcysteine - pharmacology
/ Animal tissues
/ Animals
/ Annexin V
/ Antibiotics
/ Anticancer properties
/ Antineoplastic Agents - pharmacology
/ Antioxidants - metabolism
/ Antitumor activity
/ Apoptosis
/ Apoptosis - drug effects
/ Bcl-2 protein
/ Bcl-x protein
/ Benzoquinones - pharmacology
/ Breast cancer
/ Breast carcinoma
/ Breast Neoplasms - enzymology
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Cancer
/ Care and treatment
/ Catalase
/ Cell cycle
/ Cell growth
/ Cell Line, Tumor
/ Cell Proliferation - drug effects
/ Chemical compounds
/ Development and progression
/ Doxorubicin
/ Female
/ Gene expression
/ Gene Silencing
/ Genetic aspects
/ Glutathione
/ Growth
/ Health aspects
/ Histology
/ Humans
/ Imidazoles - pharmacology
/ Immunoglobulins
/ Immunohistochemistry
/ In vivo methods and tests
/ Iodides
/ Kinases
/ Liver
/ Liver - drug effects
/ Liver - enzymology
/ MAP kinase
/ Medicine
/ Mice
/ Molecular chains
/ Oxidative stress
/ Oxidizing agents
/ p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors
/ p38 Mitogen-Activated Protein Kinases - deficiency
/ p38 Mitogen-Activated Protein Kinases - genetics
/ p38 Mitogen-Activated Protein Kinases - metabolism
/ Pharmacology
/ Phosphorylation
/ Phosphorylation - drug effects
/ Physiological aspects
/ Propidium iodide
/ Prostate
/ Proteins
/ Pyridines - pharmacology
/ Reactive Oxygen Species - metabolism
/ Staining
/ Superoxide dismutase
/ Superoxides
/ Survivin
/ Tissues
/ Tumorigenesis
/ Tumors
/ Xenograft Model Antitumor Assays
/ Xenografts
/ Xenotransplantation
/ XIAP protein
2013
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Thymoquinone Inhibits Tumor Growth and Induces Apoptosis in a Breast Cancer Xenograft Mouse Model: The Role of p38 MAPK and ROS
Journal Article
Thymoquinone Inhibits Tumor Growth and Induces Apoptosis in a Breast Cancer Xenograft Mouse Model: The Role of p38 MAPK and ROS
2013
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Overview
Due to narrow therapeutic window of cancer therapeutic agents and the development of resistance against these agents, there is a need to discover novel agents to treat breast cancer. The antitumor activities of thymoquinone (TQ), a compound isolated from Nigella sativa oil, were investigated in breast carcinoma in vitro and in vivo. Cell responses after TQ treatment were assessed by using different assays including MTT assay, annexin V-propidium iodide staining, Mitosox staining and Western blot. The antitumor effect was studied by breast tumor xenograft mouse model, and the tumor tissues were examined by histology and immunohistochemistry. The level of anti-oxidant enzymes/molecules in mouse liver tissues was measured by commercial kits. Here, we show that TQ induced p38 phosphorylation and ROS production in breast cancer cells. These inductions were found to be responsible for TQ's anti-proliferative and pro-apoptotic effects. Moreover, TQ-induced ROS production regulated p38 phosphorylation but not vice versa. TQ treatment was found to suppress the tumor growth and this effect was further enhanced by combination with doxorubicin. TQ also inhibited the protein expression of anti-apoptotic genes, such as XIAP, survivin, Bcl-xL and Bcl-2, in breast cancer cells and breast tumor xenograft. Reduced Ki67 and increased TUNEL staining were observed in TQ-treated tumors. TQ was also found to increase the level of catalase, superoxide dismutase and glutathione in mouse liver tissues. Overall, our results demonstrated that the anti-proliferative and pro-apoptotic effects of TQ in breast cancer are mediated through p38 phosphorylation via ROS generation.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Animals
/ Antineoplastic Agents - pharmacology
/ Benzoquinones - pharmacology
/ Breast Neoplasms - enzymology
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Cancer
/ Catalase
/ Cell Proliferation - drug effects
/ Female
/ Growth
/ Humans
/ Iodides
/ Kinases
/ Liver
/ Medicine
/ Mice
/ p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors
/ p38 Mitogen-Activated Protein Kinases - deficiency
/ p38 Mitogen-Activated Protein Kinases - genetics
/ p38 Mitogen-Activated Protein Kinases - metabolism
/ Phosphorylation - drug effects
/ Prostate
/ Proteins
/ Reactive Oxygen Species - metabolism
/ Staining
/ Survivin
/ Tissues
/ Tumors
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