Abstract
Retinoblastoma (Rb) is the most common primary intraocular malignant tumor of childhood. It is important to develop the strategy for Rb treatment. We have tested a quinolone derivative 2,9-bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}-11H-indeno[1,2-c]quinolin-11-one (BPIQ) for its anti-cancer effects against Rb via cultured human Rb cell line Y79. Our results showed that BPIQ significantly inhibits cell growth of Y79. Furthermore, the flow cytometer-based assays and Western blotting showed that BPIQ induces the apoptosis of Y79 via increasing the level of reactive oxygen species (ROS). Besides, the activation of γH2AX, a DNA damage sensor in human Y79 cells was also observed, indicating the potential of BPIQ for causing DNA damage of Rb cells. On the contrary, BPIQ-induced apoptosis of Y79 cells was attenuated significantly by N-acetyl-l-cysteine (NAC), an ROS scavenger. The results of Western blot showed that BPIQ down-regulates the levels of anti-apoptotic proteins Bcl-2, survivin and XIAP while up-regulates the pro-apoptotic proteins Bad, Bax and Bid. Our present study demonstrated the anti-proliferative effect of BPIQ in human Y79 cells. The inhibitory effect of BPIQ on the proliferation of Y79 cells is, at least, partly mediated by the regulation of ROS and DNA damage pathway. In conclusion, BPIQ may provide an alternative option in the chemotherapeutics or chemoprevention on the Rb therapy in the future.
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Acknowledgments
The study was financially supported by the Grants MOST101-2320-B-037-046-MY3 and MOST102-2632-B-037-001-MY3 from Ministry of Science and Technology (Taiwan); by the Grants KMHK-99-011, KMHK-100-016, KMHK-101-014, KMHK-102-011 from Kaohsiung Municipal Hsiao-kang Hospital and RG14-018 from Yuan’s General Hospital; by the grant #NSYSUKMU104-P031 from the National Sun Yat-sen University-KMU Joint Research Project; by the grant Aim for the Top Universities Grant, Grant No. KMU-TP103A17.
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Cheng, KC., Hung, CT., Chen, KJ. et al. Quinoline-Based Compound BPIQ Exerts Anti-Proliferative Effects on Human Retinoblastoma Cells via Modulating Intracellular Reactive Oxygen Species. Arch. Immunol. Ther. Exp. 64, 139–147 (2016). https://doi.org/10.1007/s00005-015-0368-4
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DOI: https://doi.org/10.1007/s00005-015-0368-4