P21Cip1 is a critical mediator of the cytotoxic action of thymidylate synthase inhibitors in colorectal carcinoma cells

• Published in: Cancer research (Chicago, Ill.) Vol. 64; no. 17; pp. 6296 - 6303
• Main Authors: GELLER, James I, SZEKELY-SZUCS, Kinga, PETAK, Istvan, DOYLE, Belinda, HOUGHTON, Janet A
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2004
• Subjects: Antineoplastic agents; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - enzymology; Cyclin-Dependent Kinase Inhibitor p21; Cyclins - biosynthesis; Cyclins - deficiency; Cyclins - metabolism; Cyclins - physiology; Drug Synergism; Enzyme Inhibitors - pharmacology; fas Receptor - biosynthesis; fas Receptor - physiology; G1 Phase - drug effects; G1 Phase - genetics; G1 Phase - physiology; HCT116 Cells; HT29 Cells; Humans; Interferon-gamma - pharmacology; Medical sciences; Pharmacology. Drug treatments; Purines - pharmacology; Quinazolines - pharmacology; S Phase - drug effects; S Phase - genetics; S Phase - physiology; Thymidylate Synthase - antagonists & inhibitors; Tumors; Rectal disease; Enzyme; Transferases; Colorectal cancer; Cytotoxicity; Malignant tumor; Thymidylate synthase; Colonic disease; Methyltransferases; Digestive diseases; Intestinal disease; Inhibitor; Mediator

We have demonstrated previously that interferon (IFN)-gamma sensitizes human colon carcinoma cell lines to the cytotoxic effects of 5-fluorouracil combined with leucovorin and to the thymidylate synthase inhibitor, ZD9331, dependent on thymineless stress-induced DNA damage, independent of p53. Here...