CHNQ, a novel 2-Chloro-1,4-naphthoquinone derivative of quercetin, induces oxidative stress and autophagy both in vitro and in vivo

Date

2016-4

Author

Enayat, Shabnam
Şeyma Ceyhan, M.
Taşkoparan, Betül
Stefek, Milan
Banerjee, Sreeparna

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Quercetin (Qc) shows strong antitumor effects but has limited clinical application due to poor water solubility and bioavailability. In a screening of novel semi-synthetic derivatives of Qc, 3,7-dihydroxy-2-[4-(2-chloro-1,4-naphthoquinone-3-yloxy)-3-hydroxyphenyl]-5-hydroxychromen-4-one (CHNQ) could ameliorate acetic acid induced acute colitis in vivo more efficiently than Qc. Since inflammation contributes to colorectal cancer (CRC), we have hypothesized that CHNQ may have anti-cancer effects. Using CRC cell lines HCT-116 and HT-29, we report that CHNQ was three-fold more cytotoxic than Qc along with a robust induction of apoptosis. As expected from naphthoquinones such as CHNQ, a strong induction of oxidative stress was observed. This was accompanied by reactive oxygen species (ROS) induced autophagy marked by a dramatic increase in the lipidation of LC3, decreased activation of Akt/PKB, acidic vesicle accumulation and puncta formation in HCT-116 cells treated with CHNQ. Interestingly, an incomplete autophagy was observed in HT-29 cells where CHNQ treatment led to LC3 lipidation, but not the formation of acidic vacuoles. CHNQ-induced cytotoxicity, ROS formation and autophagy were also detected in vivo in Saccharomyces cerevisiae strain RDKY3615 (WinstonS288C background). Overall, we propose that CHNQ can induce cancer cell death through the induction of oxidative stress, and may be examined further as a potential chemotherapeutic drug.

Subject Keywords

CHNQ, Quercetin, Colon cancer, Oxidative stress, Autophagy

URI

https://hdl.handle.net/11511/28477

Journal

Archives of Biochemistry and Biophysics

DOI

https://doi.org/10.1016/j.abb.2016.03.004

Collections

Department of Biology, Article

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Citation Formats

S. Enayat, M. Şeyma Ceyhan, B. Taşkoparan, M. Stefek, and S. Banerjee, “CHNQ, a novel 2-Chloro-1,4-naphthoquinone derivative of quercetin, induces oxidative stress and autophagy both in vitro and in vivo,” Archives of Biochemistry and Biophysics, pp. 84–98, 2016, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/28477.