Induction of apoptosis by phenylisocyanate derivative of quercetin: involvement of heat shock protein.
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.
Ye
Bin
B
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, PRC.
Yang
Jin-Liang
JL
Chen
Li-Juan
LJ
Wu
Xian-Xue
XX
Yang
Han-Shuo
HS
Zhao
Ju-Mei
JM
Yuan
Zhi-Ping
ZP
Li
Jiong
J
Wen
Yan-Jun
YJ
Mao
Yong-Qiu
YQ
Lei
Song
S
Kan
Bing
B
Fan
Lin-Yu
LY
Yao
Wen-Xiu
WX
Wang
Rui
R
Wang
Guo-Qing
GQ
Du
Xiao-Bo
XB
Liu
Huan-Yi
HY
Wu
Hong-Bing
HB
Xu
Jian-Rong
JR
Li
Hong-Xia
HX
Zhang
Wei
W
Zhao
Xia
X
Wei
Yu-Quan
YQ
Cheng
Li
L
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
D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; C526427:quercetin phenylisocyanate; D011794:Quercetin