title: Induction of apoptosis by phenylisocyanate derivative of quercetin: involvement of heat shock protein.
abstract: Quercetin, a widely distributed bioflavonoid, inhibits the growth of various tumor cells. The present study was designed to investigate whether a novel quercetin derivative [phenylisocyanate of quercetin (PHICNQ)] exerts antitumor activity against K562 and CT26 tumor cell lines by inducing apoptosis, and to examine the possible mechanism in the phenomenon. The cell proliferation assay of K562 and CT26 tumor cells was determined by the trypan blue dye exclusion test. Apoptosis of PHICNQ-treated cells was determined by morphological analysis, agarose gel DNA electrophoresis and quantitated by flow cytometry after staining with propidium iodide. Cell cycle was evaluated by flow cytometry. The expression of heat shock protein 70 was checked by Western blot analysis. Our results showed that PHICNQ inhibited the proliferation of K562 and CT26 cells in a dose-dependent and time-dependent manner. PHICNQ was 308- and 73-fold more active on CT26 and K562 cells than quercetin, respectively. In addition to this cytostatic effect, treatment of K562 and CT26 tumor cells with PHICNQ induced apoptosis. PHICNQ treatment downregulated the expression of heat shock protein 70 more dramatically than quercetin treatment. These results suggest that PHICNQ is a more powerful antiproliferative derivative than quercetin, with cytostatic and apoptotic effects on K562 and CT26 tumor cells. PHICNQ may trigger apoptosis in tumor cells through inhibition of heat shock protein 70 synthesis and expression.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, PRC.
authors: Bin
authors: B
authors: Ye
authors: Jin-Liang
authors: JL
authors: Yang
authors: Li-Juan
authors: LJ
authors: Chen
authors: Xian-Xue
authors: XX
authors: Wu
authors: Han-Shuo
authors: HS
authors: Yang
authors: Ju-Mei
authors: JM
authors: Zhao
authors: Zhi-Ping
authors: ZP
authors: Yuan
authors: Jiong
authors: J
authors: Li
authors: Yan-Jun
authors: YJ
authors: Wen
authors: Yong-Qiu
authors: YQ
authors: Mao
authors: Song
authors: S
authors: Lei
authors: Bing
authors: B
authors: Kan
authors: Lin-Yu
authors: LY
authors: Fan
authors: Wen-Xiu
authors: WX
authors: Yao
authors: Rui
authors: R
authors: Wang
authors: Guo-Qing
authors: GQ
authors: Wang
authors: Xiao-Bo
authors: XB
authors: Du
authors: Huan-Yi
authors: HY
authors: Liu
authors: Hong-Bing
authors: HB
authors: Wu
authors: Jian-Rong
authors: JR
authors: Xu
authors: Hong-Xia
authors: HX
authors: Li
authors: Wei
authors: W
authors: Zhang
authors: Xia
authors: X
authors: Zhao
authors: Yu-Quan
authors: YQ
authors: Wei
authors: Li
authors: L
authors: Cheng
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; C526427:quercetin phenylisocyanate; D011794:Quercetin