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

Metadata

Show full item record

Item Usage Stats

286
views

0
downloads

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

Suggestions

OpenMETU
Core

Benzaldehyde lyase-catalyzed enantioselective carboligation of aromatic aldehydes with mono- and dimethoxy acetaldehyde Demir, Ayhan Sıtkı; Sesenoglu, O; Dunkelmann, P; Muller, M (American Chemical Society (ACS), 2003-06-12) Benzaldehyde lyase from the Pseudomonas fluorescens catalyzes the reaction of aromatic aldehydes with methoxy and dimethoxy acetaldehyde and furnishes (R)-2-hydroxy-3-methoxy-1-arylpropan-1-one and (R)-2-hydroxy-3,3-dimethoxy-1-arylpropan-1-one in high yields and enantiomeric excess via acyloin linkage. Aromatic aldehydes and benzoins are converted into enamine-carbanion-like intermediates prior to carboligation.
Colloidal Stabilization of Submicron-Sized Zeolite NaA in Ethanol-Water Mixtures for Nanostructuring into Thin Films and Nanofibers Gözcü, Oğuz; Kayacı, H. Utkucan; Dou, Yibo; Zhang, Wenjing; Hedin, Niklas; Jasso-Salcedo, Alma B.; Kaiser, Andreas; Çınar, Simge (2023-01-10) Despite the growing use of organic or mixed solvents in zeolite processing, most studies focus only on aqueous suspension systems. We investigated the colloidal characteristics of submicron-sized zeolite NaA in mixed ethanol-water solvents. The effects of the mixing ratio of solvents and various additives on the dispersion of the zeolite powders were studied. The zeolite NaA particles were destabilized in solvent mixtures at a high ethanol-to-water ratio, a reduction in the zeta potential was observed, and ...
PFAM catalyzed enantioselective diethylzinc addition to imines Doğan, Özdemir (2015-01-01) Chiral amines are important starting materials for the synthesis of biologically important compounds. Enantioselective addition of dialkylzinc reagents to imines is a reliable method for the synthesis of these compounds. Different chiral catalysts were developed and used for this method. Phosphorous based PFAM catalysts were tried for the first time in the enantioselective synthesis of amines by reacting diethylzinc with N-sulfonyl imines and N-diphenylphosphinoyl imines. Chiral amines were isolated with mo...
Tin effect in formation and photocross-linking reactions of tri-n-butylstannyl methacrylate-allyl chloroacetate copolymer Rzaev, ZMO (Wiley, 1998-09-30) Radical-initiated copolymerization of tri-n-butylstannyl methacrylate (TBSM) with allyl chloroacetate (ACA) was carried out in the presence of benzoyl peroxide as initiator in benzene at 70 degrees C in nitrogen atmosphere. Monomer reactivity ratios of the TBSM (M-1)-ACA (M-2) monomer pair were determined by the Kelen-Tudos method: r(1) = 1.25 +/- 0.02 and r(2) = 0.13 +/- 0.005. From copolymerization kinetic data the Values of effective energy of activation (E-a) and orders with respect to initiator (n) and...
Multipurpose acetic acid functionalized carbazole derivatives: Synthesis, electrochemical properties and electrochromic device applications Özdemir Hacıoğlu, Şerife; YİĞİT, DENİZ; Akbey, Tuba E.; UDUM, YASEMİN; GÜLLÜ, MUSTAFA; DEPCİ, TOLGA; Toppare, Levent Kamil (2022-03-01) In this study, synthesis of two multifunctional acetic acid functionalized carbazole bearing monomers; 243,6-bis(2,3-dihydrothieno [3,4-b] [1,4]dioxin-5-yl)-9H-carbazol-9-yl)acetic acid (Ml) and 3,6-dithien-2-yl-9H car bazol-9-ylaceticacid (M2) via Stille cross-coupling reaction was reported. Obtained monomers were electro-chemically polymerized in 0.1 M TBAPF(6)/DCM/ACN (5:95, v:v) solution and characterized in terms of electrochemical, spectroelectrochemical and electrochromic switching behaviors. When po...

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.