Cochlioquinone derivative CoB1 induces cytostatic autophagy in lung cancer through miRNA-125b and Foxp3 |
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| Institution: | 1. Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province and School of Life Sciences, Jiangsu Normal University, Xuzhou 221116, P. R. China;2. Laboratory of Morphology, Xuzhou Medical University, Xuzhou 221004, P. R. China;3. Department of Physiology, Xuzhou Medical University, Xuzhou 221004, P. R. China;4. Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming 650500, China;5. Jiangsu Medical Engineering Research Center of Gene Detection, Xuzhou Medical University, Xuzhou 221004, P. R. China;1. Department of Human Anatomy, Histology and Embryology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215007, China;2. School of Medicine, Yangzhou University, Yangzhou 225001, China;3. Institute of Hand Surgery, Ruihua Affiliated Hospital of Soochow University, Suzhou 215007, China;1. State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou 510070, China;2. Program for Natural Products Chemical Biology, Key Laboratory of Plant Resources Conservation and Sustainable Utilization, Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China |
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| Abstract: | BackgroundLung cancer is the leading cause of cancer death worldwide, yet no effective medication for this disease is available. Cochlioquinone B derivative (CoB1), purified from Salvia miltiorrhiza endophytic Bipolaris sorokiniana, affects the defense against pulmonary pathogens by regulating inflammatory responses. However, the effect of CoB1 on lung cancer and the underlying molecular mechanisms remain unknown. In the present study, we investigate the protective effects of CoB1 on lung cancer and explore its underlying mechanism.MethodWe examined the inhibitory effect of CoB1 on lung cancer cells (A549 cells) by MTT and colony formation assay. The effect of CoB1 on cytostatic autophagy in lung cancer cells was verified by Western blot, transmission electron microscopy, and confocal microscopy. The differentially expressed miRNAs were identified using quantitative RT-PCR. Luciferase assay and Northern blot were performed to verify the correlation between miRNA-125b and Foxp3. Protein expression in autophagy-related pathways was detected by Western blot. Xenograft tumor models were constructed to explore the inhibitory effect of CoB1 and the role of miRNA-125b as a suppressor in lung cancer in vivo.ResultCoB1 inhibited lung cancer cell proliferation by inducing cytostatic autophagy both in vitro and in vivo. CoB1-induced autophagy was related to blocking of the PI3K/Akt1/mTOR signaling pathway. In addition, CoB1 induced miR-125b expression via activating the TAK1/MKK4/JNK/Smad axis, thereby reducing Foxp3 expression and further inducing autophagy.ConclusionThis study is the first to report the specific inhibitory function of CoB1 purified from Salvia miltiorrhiza endophytic Bipolaris sorokiniana in lung cancer, which may be due to the induction of autophagy. This study provides evidence and novel insights into the anticancer efficacy of CoB1. |
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