Quercetin inhibits p21-RAS expression in human colon cancer cell lines and in primary colorectal tumors.
Immunocytochemical studies have revealed that 10 microM quercetin reduced the steady state levels of p21-ras proteins in both colon cancer cell lines and primary colorectal tumors. These findings were confirmed by Western blot and flow cytometric analysis showing that the inhibition of p21-ras expression by quercetin was time- and concentration-dependent. Twenty-four-hour treatment with 10 microM quercetin reduced p21-ras levels to about 50% of control values. Quercetin was similarly effective in inhibiting the expression of K-, H-, and N-ras proteins. Moreover, the effect of quercetin on ras oncogene expression was not dependent on the cell cycle position of colon cancer cells and appeared to be specific and not merely a consequence of overall inhibition of protein synthesis. Northern blot analysis revealed that quercetin produced in colon cancer cells an early (30 min) reduction of the steady state levels of K-, H-, and N-ras mRNAs. This reduction was also present after 6 hr of flavonoid treatment. These effects of quercetin suggest a possible chemopreventive role for this compound in colorectal carcinogenesis.
Ranelletti
F O
FO
Institute of Histology, Università Cattolica del S. Cuore, Roma, Italy. ibiap@rm.unicatt.it
Maggiano
N
N
Serra
F G
FG
Ricci
R
R
Larocca
L M
LM
Lanza
P
P
Scambia
G
G
Fattorossi
A
A
Capelli
A
A
Piantelli
M
M
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D011905:Genes, ras / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects; D012334:RNA, Neoplasm / Q000187:drug effects; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011794:Quercetin