Antitumor effects of 3-bromoascochlorin on small cell lung cancer via inhibiting MAPK pathway |
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| Authors: | Zhenhua Zhang Yidi Zhang Chunju Yang Qianyu Wang Hong Wang Yanting Zhang Wenbin Deng Yichu Nie Yonghong Liu Xiaowei Luo Jie Huang Junjian Wang |
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| Affiliation: | 1. School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, China;2. Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangdong Province Engineering Laboratoty for Druggability and New Drug Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China;3. Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China;4. Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning, China;5. CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, China |
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| Abstract: | Small cell lung cancer (SCLC) was defined as a recalcitrant cancer, and novel therapies are urgently needed. Marine natural products (MNPs) may bring continuing hope for treatment of SCLC. In this study, 3-bromoascochlorin (BAS), an MNP isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501, was primarily screened out with antiproliferative activity towards SCLC cell lines. Then western blot analysis (WB) and flow cytometry were conducted, and we found BAS could induce the apoptosis of H446 and H69AR cells. Besides, BAS could suppress the invasion and migration of H446. In an SCLC xenograft mice model, BAS inhibited the growth of tumor without affecting the body weight of mice. Finally, the underlying mechanisms were preliminarily explored. According to the results of RNA-seq, reverse transcription-quantitative polymerase chain reaction, and WB, our results revealed that BAS exerted antitumor activity via inhibiting mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) pathway. Collectively, these results indicated that BAS can be used as a promising compound for the treatment of human SCLC. |
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| Keywords: | ascochlorin FGFR1 MAPK/ERK pathway marine natural product small cell lung cancer |
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