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03 June 2018 : Laboratory Research  

Quinalizarin Induces Apoptosis through Reactive Oxygen Species (ROS)-Mediated Mitogen-Activated Protein Kinase (MAPK) and Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathways in Colorectal Cancer Cells

Ling-Qi Meng1BE, Yue Wang2B, Ying-Hua Luo3C, Xian-Ji Piao4D, Chang Liu1C, Yue Wang1C, Yi Zhang1B, Jia-Ru Wang1B, Hao Wang1C, Wan-Ting Xu1B, Yang Liu1C, Yi-Qin Wu1B, Hu-Nan Sun1E, Ying-Hao Han1E, Mei-Hua Jin1F, Gui-Nan Shen1E, Nan-Zhu Fang5A, Cheng-Hao Jin1AG*

DOI: 10.12659/MSM.907163

Med Sci Monit 2018; 24: LBR3710-3719

Abstract

BACKGROUND: Quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) exhibits potentially useful anticancer effects by inducing apoptosis in several types of cancer, but its underlying mechanism of action remains unknown. The present study examined the effects of quinalizarin on the induction of cell cycle arrest, apoptosis, the generation of reactive oxygen species (ROS), other underlying mechanisms, and its role in modifying colorectal cancer cell lines.

MATERIAL AND METHODS: The MTT assay was used to evaluate the viability of SW480 and HCT-116 cells that had been treated with quinalizarin and 5-fluorouracil (5-FU). Cell cycle arrest and apoptosis were analyzed by flow cytometry. Western blotting was used to investigate the mitochondrial pathway; Akt, MAPK, and STAT3 signaling pathways were also investigated. The relationship between ROS generation and apoptosis was analyzed by flow cytometry and western blotting.

RESULTS: The results indicated that quinalizarin significantly inhibits the viability of SW480 and HCT-116 cells in a dose-dependent manner. Quinalizarin induced SW480 cell cycle arrest at G2/M by regulating cyclin B1 and CDK1/2. The apoptosis-related protein expression levels of p-p53, Bad, cleaved caspase-3, cleaved PARP and p-JNK were increased in quinalizarin-treated cells, while protein expression levels Bcl-2, p-Akt, p-ERK, and p-STAT3 were decreased. Quinalizarin induced apoptosis in colorectal cancer cells by regulating MAPK and STAT3 signaling pathways via ROS generation.

CONCLUSIONS: Quinalizarin induces apoptosis via ROS-mediated MAPK/STAT3 signaling pathways.

Keywords: Colorectal Neoplasms, Mitogen-Activated Protein Kinases, STAT3 Transcription Factor

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750