Abstract
Objective
Zunyimycin C is a novel halogenated type II polyketide derived from the fermentation product of the Streptomyces species with notable antibiotic activity. However, it is still unclear whether zunyimycin C could inhibit the activity of cancer cells. In this study, human lung adenocarcinoma cell line A549, the large-cell lung cancer cell line NCI-H460 and the non-small-cell lung cancer cell line NCI-H1299 were employed to determine the in vitro anticancer properties of zunyimycin C and underlying molecular mechanisms.
Materials and methods
The cellular viability and proliferative properties of lung cancer cells were investigated using the Cell Counting Kit-8 and colony formation assay, respectively. The mRNA expression of apoptotic genes related to lung cancer was studied using reverse-transcription polymerase chain reaction. The apoptotic ratio was measured through flow cytometry. The protein expression was visualized via western blotting using specific antibodies.
Results
Zunyimycin C could inhibit cell proliferation and induce apoptosis in a dose-dependent manner. The expression levels of apoptosis-related proteins (i.e., BAX, cleaved-caspase-3, and cleaved-caspase-9) were increased compared with the control group. However, the levels of Bcl-2 and phosphorylated AKT were decreased by administration by zunyimycin C.
Conclusions
Collectively, these results implied that zunyimycin C could inhibit cell proliferation and induce apoptosis via AKT phosphorylation.
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Acknowledgements
The Authors would like to thank Yun Liu for his assistance with flow cytometry and Sanhua Li for her technical assistance. Especially, thanks to Changwu Yue for providing test compound of zunyimycin C. This work was funded by the National Nature Science Foundation of China (Grant no. 31460006), the Science and Technology Foundation of Guizhou Province (no. (2013) 3013).
Authors’ contributions
Study design: YB. Data acquisition: WL. Data analysis and interpretation: YB, ZQ, and WL. Statistical analysis: WL. Manuscript writing: WL. Manuscript editing: YB, ZQ. Manuscript review: WL, JZ, WW, YB, and ZQ.
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Li, W., Zheng, J., Wang, W. et al. Zunyimycin C inhibits the proliferation of lung cancer cells by inducing apoptosis through an AKT-related mechanism. Med Chem Res 28, 1828–1837 (2019). https://doi.org/10.1007/s00044-019-02417-2
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DOI: https://doi.org/10.1007/s00044-019-02417-2