Albanian
Arabic
Armenian
Azerbaijani
Belarusian
Bengali
Bosnian
Catalan
Czech
Danish
Deutsch
Dutch
English
Estonian
Finnish
Français
Greek
Haitian Creole
Hebrew
Hindi
Hungarian
Icelandic
Indonesian
Irish
Italian
Japanese
Korean
Latvian
Lithuanian
Macedonian
Mongolian
Norwegian
Persian
Polish
Portuguese
Romanian
Russian
Serbian
Slovak
Slovenian
Spanish
Swahili
Swedish
Turkish
Ukrainian
Vietnamese
Български
中文(简体)
中文(繁體)
Chemical Research in Toxicology 2012-Nov

A cysteine-reactive alkyl hydroquinone modifies topoisomerase IIα, enhances DNA breakage, and induces apoptosis in cancer cells.

Samo registrirani korisnici mogu prevoditi članke
Prijava Registriraj se
Veza se sprema u međuspremnik
Ting-Yu Lin
Cheng-Po Huang
Lo-Chun Au
Ya-Wen Chang
Chung-Yi Hu
Shwu-Bin Lin

Ključne riječi

Sažetak

We previously reported that the anticancer activity of a botanical compound 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone [HQ17(3)] was attributed to topoisomerase (Topo) IIα poisoning and the induction of oxidative damage. HQ17(3) irreversibly inhibits Topo IIα activity in vitro and is more cytotoxic in leukemia HL-60 cells than in Topo IIα-deficient variant HL-60/MX2 cells, which suggests that Topo IIα is a cellular target of HQ17(3). This study further characterizes the molecular mechanisms of the anticancer activity of HQ17(3). Proteomic analyses indicated that HQ17(3) reacted with Cys-427, Cys-733, and Cys-997 of recombinant Topo IIα in vitro, whereas it reacted with Cys-427 of cellular Topo IIα in Huh7 hepatoma cells. The modification of HQ17(3) inhibited Topo IIα catalytic activity, increased the Topo IIα-DNA cleavage complex, and caused the accumulation of DNA breakage. In Huh7 cells, HQ17(3) treatment caused prompt inhibition of DNA synthesis and consequently induced the expression of DNA damage-related genes DDIT3, GADD45A, and GADD45G. Topo IIα inhibition, apoptosis, and oxidative stress were found to account for cytotoxicity caused by HQ17(3). Pretreatment of Huh7 cells with N-acetylcysteine (NAC) partially attenuated mitochondrial membrane damage, DNA breakage, and caspase activation. However, NAC pretreatment did not diminish HQ17(3)-induced cell death. These results suggest that the anticancer activity of HQ17(3) is attributed significantly to Topo IIα poisoning. The structural feature of HQ17(3) can be used as a model for the design of Topo IIα inhibitors and anticancer drugs.

Pridružite se našoj
facebook stranici

Najkompletnija baza ljekovitog bilja potpomognuta znanošću

  • Radi na 55 jezika
  • Biljni lijekovi potpomognuti znanošću
  • Prepoznavanje bilja slikom
  • Interaktivna GPS karta - označite bilje na mjestu (uskoro)
  • Pročitajte znanstvene publikacije povezane s vašom pretragom
  • Pretražite ljekovito bilje po učincima
  • Organizirajte svoje interese i budite u toku s istraživanjem vijesti, kliničkim ispitivanjima i patentima

Upišite simptom ili bolest i pročitajte o biljkama koje bi mogle pomoći, unesite travu i pogledajte bolesti i simptome protiv kojih se koristi.
* Svi podaci temelje se na objavljenim znanstvenim istraživanjima

Google Play badgeApp Store badge