Enhancement of human cancer cell radiosensitivity by conjugated eicosapentaenoic acid - a mammalian DNA polymerase inhibitor.
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.
Kumamoto-Yonezawa
Yuko
Y
Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan.
Sasaki
Ryohei
R
Suzuki
Yoko
Y
Matsui
Yuki
Y
Hada
Takahiko
T
Uryu
Keisuke
K
Sugimura
Kazuro
K
Yoshida
Hiromi
H
Mizushina
Yoshiyuki
Y
D017304:Annexin A5 / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D019384:Nucleic Acid Synthesis Inhibitors; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D016896:Treatment Outcome
D017304:Annexin A5; D000970:Antineoplastic Agents; D019384:Nucleic Acid Synthesis Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D015118:Eicosapentaenoic Acid; D004259:DNA-Directed DNA Polymerase; C022616:thiazolyl blue