Enhancement of human cancer cell radiosensitivity by conjugated eicosapentaenoic acid - a mammalian DNA polymerase inhibitor.

Abstract	We previously found that conjugated eicosapentaenoic acid (cEPA) selectively inhibited the activities of mammalian DNA polymerases (pols), and suppressed human cancer cell growth. The aim of the present study was to evaluate the efficacy of concurrent radiation with cEPA in a human colon carcinoma cell line, HCT 116. Furthermore, we examined the most effective timing of irradiation. The post-irradiation addition of cEPA significantly enhanced HCT116 cell radiosensitivity by decreasing the expression of pols beta, delta and epsilon, increasing damaged DNA, such as DNA double-strand breaks, inhibiting clonogenic survival, and inducing apoptosis. However, cells treated by pre-irradiation addition of cEPA did not influence radiosensitive survival and radiation-induced apoptosis. cEPA inhibited the activities of pols needed for DNA repair, thereby DNA damage must be augmented by cEPA and irradiation. These results suggested that the combination of inhibitors of DNA repair-related pols/radiation could be an effective anticancer therapy.
Authors	Yuko Kumamoto-Yonezawa, Ryohei Sasaki, Yoko Suzuki, Yuki Matsui, Takahiko Hada, Keisuke Uryu, Kazuro Sugimura, Hiromi Yoshida, Yoshiyuki Mizushina
Journal	International journal of oncology (Int J Oncol) Vol. 36 Issue 3 Pg. 577-84 (Mar 2010) ISSN: 1791-2423 [Electronic] Greece
PMID	20126977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Annexin A5 Antineoplastic Agents Nucleic Acid Synthesis Inhibitors Tetrazolium Salts Thiazoles Eicosapentaenoic Acid DNA-Directed DNA Polymerase thiazolyl blue
Topics	Annexin A5 (pharmacology) Antineoplastic Agents (pharmacology) Apoptosis Cell Line, Tumor Colonic Neoplasms Comet Assay DNA Damage DNA Repair DNA-Directed DNA Polymerase (metabolism) Dose-Response Relationship, Drug Eicosapentaenoic Acid (pharmacology) Humans Neoplasms (radiotherapy) Nucleic Acid Synthesis Inhibitors Tetrazolium Salts (pharmacology) Thiazoles (pharmacology) Treatment Outcome

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