Jeremy Yee Hoong Ong1, Phelim Voon Chen Yong1, Yang Mooi Lim2, Anthony Siong Hock Ho3. 1. School of Biosciences, Taylor's University, No. 1, Jalan Taylor's, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia. 2. Department of Pre-Clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Lot PT21144, Jalan Sungai Long, Bandar Sungai Long, 43000 Kajang, Selangor Darul Ehsan, Malaysia. 3. School of Biosciences, Taylor's University, No. 1, Jalan Taylor's, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia. Electronic address: anthony.ho@taylors.edu.my.
Abstract
AIM: The compound 2-methoxy-1,4-naphthoquinone (MNQ) was previously shown to be cytotoxic against several cancer cell lines, but its mode of action is poorly understood. In this study, we aimed to explore the molecular mechanism of MNQ-induced cytotoxicity of A549 lung adenocarcinoma cells. MAIN METHODS: The growth inhibition potential of MNQ was analyzed using sulforhodamine B assay, flow cytometry cell cycle analysis and Annexin V apoptosis assay. Oxidative stress was determined using 2',7'-dichlorofluorescein diacetate to measure intracellular reactive oxygen species level and comet assay to measure DNA damage. Western blotting was performed to study the activation of mitogen-activated protein kinase signaling pathways. KEY FINDINGS: MNQ induced apoptosis of A549 cells independent of cell cycle arrest, and is mediated by the JNK and p38 MAPK signaling pathways. Further analysis demonstrated that these signaling pathways were stimulated by oxidative DNA damage caused by increased ROS generation in MNQ-treated A549 cells. SIGNIFICANCE: This study is the first to provide an insight into the molecular mechanism of MNQ-induced cytotoxicity of a lung cancer cell, which demonstrates the potential of MNQ as a potential chemotherapeutic drug for lung cancer treatment.
AIM: The compound 2-methoxy-1,4-naphthoquinone (MNQ) was previously shown to be cytotoxic against several cancer cell lines, but its mode of action is poorly understood. In this study, we aimed to explore the molecular mechanism of MNQ-induced cytotoxicity of A549 lung adenocarcinoma cells. MAIN METHODS: The growth inhibition potential of MNQ was analyzed using sulforhodamine B assay, flow cytometry cell cycle analysis and Annexin V apoptosis assay. Oxidative stress was determined using 2',7'-dichlorofluorescein diacetate to measure intracellular reactive oxygen species level and comet assay to measure DNA damage. Western blotting was performed to study the activation of mitogen-activated protein kinase signaling pathways. KEY FINDINGS:MNQ induced apoptosis of A549 cells independent of cell cycle arrest, and is mediated by the JNK and p38 MAPK signaling pathways. Further analysis demonstrated that these signaling pathways were stimulated by oxidative DNA damage caused by increased ROS generation in MNQ-treated A549 cells. SIGNIFICANCE: This study is the first to provide an insight into the molecular mechanism of MNQ-induced cytotoxicity of a lung cancer cell, which demonstrates the potential of MNQ as a potential chemotherapeutic drug for lung cancer treatment.
Authors: Scott B Vafai; Emily Mevers; Kathleen W Higgins; Yevgenia Fomina; Jianming Zhang; Anna Mandinova; David Newman; Stanley Y Shaw; Jon Clardy; Vamsi K Mootha Journal: PLoS One Date: 2016-09-13 Impact factor: 3.240
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Authors: Lian Chee Foong; Jian Yi Chai; Anthony Siong Hock Ho; Brandon Pei Hui Yeo; Yang Mooi Lim; Sheh May Tam Journal: Sci Rep Date: 2020-09-30 Impact factor: 4.379