(2E)-1-(2,4,6-Trimethoxyphenyl)-3-(4-chlorophenyl)prop-2-en-1-one,a Chalcone Derivative,Promotes Apoptosis by Suppressing RAS-ERK and AKT/FOXO3a Pathways in Hepatocellular Carcinoma Cells |
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Authors: | Meigui Zhang Jing Li Ruixia Ma Jiahui Xi Lili Xi Baoxin Zhang Jing Tian Zhongtian Bai |
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Institution: | 1. The First Clinical Medical School, the First Hospital of Lanzhou University, Lanzhou University, Lanzhou, 730000 China
Department of Orthopedics, >2. Gansu Provincial Hospital, Lanzhou, 730020 China;3. The First Clinical Medical School, the First Hospital of Lanzhou University, Lanzhou University, Lanzhou, 730000 China;4. Office of Institution of Drug Clinical Trail, the First Hospital of Lanzhou University, Lanzhou, 730030 China;5. State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000 China;6. Ophthalmology Department, The Second Hospital of Lanzhou University, Lanzhou, 730030 China |
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Abstract: | Background : Liver cancer is an extremely common cancer with the highest mortality rate and poor prognosis. Owing to their low systemic toxicity and few side effects, natural compounds may provide better therapeutic effects for patients. (2E)-1-(2,4,6-trimethoxyphenyl)-3-(4-chlorophenyl)prop-2-en-1-one (TMOCC), a chalcone derivative, exhibits cytotoxicity towards many tumor cells. However, the anticancer mechanism of TMOCC has not been elucidated in human hepatocellular carcinoma (HCC). Methods : Cell Counting Kit-8 and colony formation assays were used to evaluate the effects of TMOCC on viability and proliferation. Mitochondrial transmembrane potential and flow cytometry assays were used to detect apoptosis. The expression levels of proteins related to apoptosis, the RAS-ERK and AKT/FOXO3a signaling pathways were assessed using western blot. Potential targets of TMOCC were detected using molecular docking analysis. Results : TMOCC inhibited viability and proliferation, and induced the loss of mitochondrial transmembrane potential, apoptosis and DNA double-strand breaks in both HCC cells. The RAS-ERK and AKT/FOXO3a signaling pathways were suppressed by TMOCC. Finally, ERK1, PARP-1, and BAX were identified as potential targets of TMOCC. Conclusion : Taken together, our results show that TMOCC promotes apoptosis by suppressing the RAS-ERK and AKT/FOXO3a signaling pathways. TMOCC may be a potential multi-target compound that is effective against liver cancer. |
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Keywords: | chalcone derivative apoptosis ERK/MAPK pathway AKT/FOXO3a signaling pathway hepatocellular carcinoma |
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