QUERCETIN DOWN-REGULATES SIGNAL BREAST-CARCINOMA TRANSDUCTION IN HUMAN-CELLS

被引:106
作者
SINGHAL, RL
YEH, YA
PRAJDA, N
OLAH, E
SLEDGE, GW
WEBER, G
机构
[1] INDIANA UNIV,SCH MED,EXPTL ONCOL LAB,INDIANAPOLIS,IN 46202
[2] INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202
[3] RANBAXY RES LABS,NEW DRUG DISCOVERY RES,NEW DELHI 110017,INDIA
[4] NATL ONCOL INST,H-1525 BUDAPEST,HUNGARY
关键词
D O I
10.1006/bbrc.1995.1355
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Signal transduction activity was markedly elevated in cancer cells as shown by the increased activity of enzymes utilizing 1-phosphatidylinositol, PI (PI 4-kinase and PI-4-phosphate 5-kinase) for the production of the second messenger inositol 1,4,5-trisphosphate, IP3, in rat hepatomas (Cancer Res. 54:2611; 5574, 1994) and in human ovarian and breast carcinoma cells (Life Sci. 55:1487, 1994). Quercetin, a flavonoid, in human breast carcinoma MDA-MB-435 cells produced growth inhibition (IC50 = 55 mu M) and cytotoxicity (LC(50) = 26 mu M). Quercetin inhibited PI kinase activity in extracts of breast carcinoma cells (IC50 = 6 mu M) and in cultured cells (IC50 = 10 mu M) with a minor inhibition of PIP kinase activity. IP3 concentration decreased in parallel with PI kinase activity. In time sequence studies quercetin in breast carcinoma cells brought down PI kinase and IP3 concentration in 60 min to 5 and 6%, respectively; PIP kinase activity was at 63% of controls. The results demonstrate for the first time in proliferating human breast carcinoma cells a reduction by quercetin of the increased capacity for signal transduction, thus providing a novel and sensitive target in cancer cells. (C) 1995 Academic Press, Inc.
引用
收藏
页码:425 / 431
页数:7
相关论文
共 15 条
[1]   QUERCETIN AND RUTIN AS INHIBITORS OF AZOXYMETHANOL-INDUCED COLONIC NEOPLASIA [J].
DESCHNER, EE ;
RUPERTO, J ;
WONG, G ;
NEWMARK, HL .
CARCINOGENESIS, 1991, 12 (07) :1193-1196
[2]  
FISHER B, 1993, CANC MED, V2, P1706
[3]   DISPOSITION OF QUERCETIN IN MAN AFTER SINGLE ORAL AND INTRAVENOUS DOSES [J].
GUGLER, R ;
LESCHIK, M ;
DENGLER, HJ .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1975, 9 (2-3) :229-234
[4]   FLAVONOIDS, A CLASS OF NATURAL-PRODUCTS OF HIGH PHARMACOLOGICAL POTENCY [J].
HAVSTEEN, B .
BIOCHEMICAL PHARMACOLOGY, 1983, 32 (07) :1141-1148
[5]   ENHANCEMENT OF THE ANTIPROLIFERATIVE ACTIVITY OF CIS-DIAMMINEDICHLOROPLATINUM(II) BY QUERCETIN [J].
HOFMANN, J ;
FIEBIG, HH ;
WINTERHALTER, BR ;
BERGER, DP ;
GRUNICKE, H .
INTERNATIONAL JOURNAL OF CANCER, 1990, 45 (03) :536-539
[6]   INHIBITION OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE-INDUCED TUMOR PROMOTION AND ORNITHINE DECARBOXYLASE ACTIVITY BY QUERCETIN - POSSIBLE INVOLVEMENT OF LIPOXYGENASE INHIBITION [J].
KATO, R ;
NAKADATE, T ;
YAMAMOTO, S ;
SUGIMURA, T .
CARCINOGENESIS, 1983, 4 (10) :1301-1305
[7]  
KERR DJ, 1994, COMMUNICATION
[8]  
LOWRY OH, 1951, J BIOL CHEM, V193, P265
[9]   SCREENING OF PHOSPHATIDYLINOSITOL KINASE INHIBITORS FROM STREPTOMYCES [J].
NISHIOKA, H ;
IMOTO, M ;
SAWA, T ;
HAMADA, M ;
NAGANAWA, H ;
TAKEUCHI, T ;
UMEZAWA, K .
JOURNAL OF ANTIBIOTICS, 1989, 42 (05) :823-825
[10]  
PRAJDA N, 1995, UNPUB