Inhibition of cytosolic phospholipase A2 mRNA expression: a novel mechanism for acetylsalicylic acid-mediated growth inhibition and apoptosis in colon cancer cells.
Acetylsalicylic acid (ASA) has been confirmed to inhibit proliferation and to induce apoptosis in human colorectal cancer cells in vitro. However, the mechanism by which ASA exhibits antiproliferative and proapoptotic effects in cyclooxygenase 2 (COX-2)-negative cells remains to be further elucidated. In the present study, SW480, a COX-2-negative colon cancer cell line, was treated with various concentrations of ASA (0, 2.5, 5, and 10 mM). The antiproliferative and proapoptotic effects of ASA were confirmed by MTT assay, flow cytometry of propidium iodide (PI)-stained cells, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. After treatment with ASA, intracellular cyclic AMP (cAMP) levels were increased and the production of prostaglandin E2 (PGE2) was decreased. RT-PCR analysis revealed that treatment of ASA induced a concentration-dependent downregulation of cytosolic phospholipase A2 (cPLA2) mRNA expression in SW480 cells and also in two other colorectal cancer cell lines, Colo320 and HT-29 cells. Intracellular calcium levels were unaffected by ASA treatment. Our results indicate that the ASA-induced downregulation of cytosolic phospholipase A2 mRNA expression might be a novel mechanism for ASA-mediated growth inhibition and apoptosis in colon cancer cells.
Yu
Hong-Gang
HG
Department of Gastroenterology, Renmin Hosptial of Wuhan University, China.
Huang
Jie-An
JA
Yang
Yan-Ning
YN
Luo
He-Sheng
HS
Yu
Jie-Ping
JP
Meier
Juris J
JJ
Schrader
Henning
H
Bastian
Andreas
A
Schmidt
Wolfgang E
WE
Schmitz
Frank
F
D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology*; D017931:DNA Primers; D006801:Humans; D010741:Phospholipases A / Q000235:genetics*; D054467:Phospholipases A2; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D012333:RNA, Messenger; D000242:Cyclic AMP; D010741:Phospholipases A; D054467:Phospholipases A2; D001241:Aspirin