A novel aza-naphthoquinone inhibits tumor growth by inducing apoptosis

doi:10.5246/jcps.2018.09.061

Abstract

Abstract:

Natural product menaquinone has been reported to exhibit antitumor activity mediated by inhibiting IDO-1 enzyme, and naphthoquinone compounds like pyranaphthoquinone have attracted extensive research interests since they share the naphthoquinone pharmacophores. In the present study, a novel series of aza-naphthoquinones was synthesized based on 6,7-dichloroquinoline-5,8-dione structure, and their cytotoxicities were screened using lung cancer cells. Among them CY-26-11was identified as the most potent one. CY-26-11 concentration-dependently induced apoptosis in A549 human lung adenocarcinomacells, as indicated by annexin-V staining. Further experimental data show that CY-26-11 down-regulated Bcl-2 while up-regulatedBax and Puma protein levels, and activated caspase-3. Finally, CY-26-11 significantly inhibited the growth of Lewis lung carcinomaxenografts in vivo without significant major toxicities. Taken together, our results demonstrate that CY-26-11 exhibited IDO-1-independent anti-tumor effects both in vitro and in vivo, providing a new anti-tumor mechanism for naphthoquinonecompounds.

Key words: Naphthoquinone, CY-26-11, Apoptosis, Anti-tumor activity

CLC Number:

R915

Supporting:

Li Lei, Yu Chen, Simin Yang, Xiangbao Meng, Siwang Yu. A novel aza-naphthoquinone inhibits tumor growth by inducing apoptosis[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(9): 600-607.

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