A Naphthoquinone Compound Triggers Dna Damage-induced Apoptosis on Cholangiocarcinoma Through Upregulation of Bax and DR5

Background: Cholangiocarcinoma (CCA), a devastating malignancy originating from the bile ducts, is of significant clinical importance due to its rising incidence and poor prognosis. Quinones as being naturally occurring compounds and their being highly used in anticancer drug development studies seem to be potential sources for this aim. In this study, a synthetic naphthoquinone derivative, MK13, has been tested against CCA (CCLP1 and HUCCT1) cell lines. Methods: Cell viability and proliferation rate were measured with MTT assay at the doses ranged from 1.56 to 50 µM for 48h treatment. Apoptotic cell death was showed morphologically with fluorescent double staining and biochemically with flow cytometry analysis of phosphatidylserine translocation. Oxidative stress and DNA damage were also measured with flow cytometry while gene expressions were interpreted via qPCR analysis. Results: MK13 exhibited strong antigrowth activity, especially against CCLP1 cells. Cell death resulted from apoptosis that was shown to be triggered by severe DNA damage which is independent of oxidative stress. Apoptosis was confirmed at molecular level with the upregulation of BAX , a proapoptotic BH-3 only protein, and DR5 , a cell surface death receptor. Conclusion: MK13 seems to be a promising anticancer compound against CCA and deserves further in vivo studies for proof of concept.