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Titolo:
Inhibition of activator protein 1 activity and cell growth by purified green tea and black tea polyphenols in H-ras-transformed cells: Structure-activity relationship and mechanisms involved
Autore:
Chung, JY; Huang, CS; Meng, XF; Dong, ZG; Yang, CS;
Indirizzi:
Rutgers State Univ, Coll Pharm, Canc Res Lab, Piscataway, NJ 08854 USA Rutgers State Univ Piscataway NJ USA 08854 Lab, Piscataway, NJ 08854 USA Univ Minnesota, Hormel Inst, Austin, MN 55912 USA Univ Minnesota Austin MN USA 55912 ota, Hormel Inst, Austin, MN 55912 USA
Titolo Testata:
CANCER RESEARCH
fascicolo: 18, volume: 59, anno: 1999,
pagine: 4610 - 4617
SICI:
0008-5472(19990915)59:18<4610:IOAP1A>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
MOUSE EPIDERMAL-CELLS; PROLINE-RICH PROTEINS; AP-1 DNA-BINDING; NF-KAPPA-B; TUMOR PROGRESSION; SKIN TUMORS; KINASE; JUN; EXPRESSION; CANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Yang, CS Rutgers State Univ, Coll Pharm, Canc Res Lab, 164 Frelinghuysen Rd, Piscataway, NJ 08854 USA Rutgers State Univ 164 Frelinghuysen Rd Piscataway NJ USA 08854 A
Citazione:
J.Y. Chung et al., "Inhibition of activator protein 1 activity and cell growth by purified green tea and black tea polyphenols in H-ras-transformed cells: Structure-activity relationship and mechanisms involved", CANCER RES, 59(18), 1999, pp. 4610-4617

Abstract

Ras gene mutation, which perpetually turns on the growth signal transduction pathway, occurs frequently in many cancer types. The mouse epidermal JB6cell line has been transfected with a mutant H-ras gene to mimic carcinogenesis in vitro. These transformed cells (30.7b Ras 12) are able to grow in soft agar, exhibiting anchorage independence and high endogenous activator protein 1 (AP-1) activity, which can be detected by a stable AP-1 luciferase reporter. The present study investigated the ability of different pure green and black tea polyphenols to inhibit this res signaling pathway. The major green tea polyphenols (catechins), (-)-epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin, (-)-epicatechin3-gallate, (-)-epicatechin, and their epimers, and black tea polyphenols, theaflavin, theaflavin-3-gallate, theaflavin-3'-gallate, and theaflavin-3,3'-digallate (TFdiG), were compared with respect to their ability to inhibit the growth of 30.7b Ras 12 cells and AP-1 activity. All of the tea polyphenols except (-)-epicatechin showed strong inhibition of cell growth and AP-1 activity. Among the catechins, both the galloyl structure on the B ring and the gallate moiety contributed tothe growth inhibition and AP-1 activity; the galloyl structure appeared tohave a stronger effect on the inhibitory action than the gallate moiety. The epimers of the catechins showed similar inhibitory effects on AP-1 activity, The addition of catalase to the incubation of the cells with EGCG or TFdiG did not prevent the inhibitory effect on AP-1 activity, suggesting that H2O2 does not play a significant role in the inhibition by tea polyphenols. Both EGCG and TFdiG inhibited the phosphorylation of p44/42 (extracellular signal-regulated kinase 1 and 2) and c-jun without affecting the levels of phosphorylated-c-jun-NH2-terminal kinase. TFdiG inhibited the phosphorylation of p38, but EGCG did not, EGCG lowered the level of c-jun, whereas TFdiG decreased the level of fra-1. These results suggest that tea polyphenols inhibited AP-1 activity and the mitogen-activated protein kinase pathway,which contributed to the growth inhibition; however, different mechanisms may be involved in the inhibition by catechins and theaflavins.

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Documento generato il 22/01/20 alle ore 12:55:18