Zunyimycin C inhibits the proliferation of lung cancer cells by inducing apoptosis through an AKT-related mechanism
- 24 Downloads
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.
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.
Collectively, these results implied that zunyimycin C could inhibit cell proliferation and induce apoptosis via AKT phosphorylation.
KeywordsZunyimycin C Lung cancer Cell proliferation inhibition AKT Apoptosis
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).
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Chen W, Zheng R, Baade PD et al. (2016) Cancer statistics in China, 2015. Cancer J Clin 66(2):115–132Google Scholar
- Li JS, Zhang H, Qi H et al. (2018) Bioactive naphthoquinone and anthrone derivatives from endophytic Micromonospora sp. NEAU-gq13. J Asian Nat Prod Res 26:1–10Google Scholar
- Torre LA, Bray F, Siegel RL et al. (2015) Global cancer statistics, 2012. Cancer J Clin 65:87–108Google Scholar
- Wang M, Li Y, Shao M et al. (2014) Separation and phylogenetic analysis of actinomycetes with activity of against Candida albicans from Chishui danxia soil. J Zunyi Med Univ 37(4):404–408.Google Scholar
- Wang Y, Shao M, Yue C (2016) Research development of halogenated natural products derived microorganisms. J Zunyi Med Univ 39(4):435–440.Google Scholar
- Yu P, Shi L, Song M, Meng Y (2017) Antitumor activity of paederosidic acid in human non-small cell lung cancer cells via inducing mitochondria-mediated apoptosis. Chem Biol Inter 269:33–40Google Scholar
- Zhou L, Wu F, Jin W et al. (2017) Theabrownin inhibits cell cycle progression and tumor growth of lung carcinoma through c-myc-related mechanism. Front Pharm 8:75Google Scholar
- Zhou R, Chen H, Chen J et al. (2018) Extract from Astragalus membranaceus inhibit breast cancer cells proliferation via PI3K/AKT/mTOR signaling pathway. BMC Complement Alter Med 18:83Google Scholar