Albumin modulates docosahexaenoic acid-induced cytotoxicity in human hepatocellular carcinoma cell lines.
Fish oil-containing diets rich in cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) provide protection against tumorigenesis. The mechanisms of the cytotoxic effects of DHA include the production of reactive oxygen species (ROS). Albumin has antioxidant property and binds fatty acids, it may protect the cells against the DHA-induced cytotoxicity. In this study, we compared the susceptibility of three human hepatocellular carcinoma (HCC) cell lines (HepG2, Hep3B, Huh7) to the cytotoxic effects of DHA, and examined the changes in the susceptibility following albumin overexpression using transfection vectors or albumin downregulation using small interfering RNA (siRNA). HepG2 cells were the most susceptible to DHA-induced cytotoxicity and increased oxidative activities by DHA compared to Hep3B and Huh7 cells. The cytotoxic effects of DHA were concentration-dependently abrogated by typical antioxidants, a radical scavenger, an iron chelator and incubation with exogenous albumin. Overexpression of albumin in HepG2 cells markedly attenuated DHA-induced oxidative activities and cytotoxicity. Furthermore, knockdown of albumin in both Hep3B and Huh7 cells significantly enhanced the effects of DHA. The results of our in vitro experiments indicate that the cytotoxic effects of DHA on HCC cell lines are modulated by albumin.
Department of Clinical Pharmacotherapeutics, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aobaku, Sendai 981-8558, Japan. syu-kan@tohoku-pharm.ac.jp
Syu-ichi
S
Kanno
Kaori
K
Kurauchi
Ayako
A
Tomizawa
Shin
S
Yomogida
Masaaki
M
Ishikawa
D000418:Albumins / Q000494:pharmacology*; D000970:Antineoplastic Agents; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D004396:Coloring Agents; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D004281:Docosahexaenoic Acids / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007502:Iron Chelating Agents / Q000494:pharmacology; D010084:Oxidation-Reduction; D010957:Plasmids / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014162:Transfection
D000418:Albumins; D000970:Antineoplastic Agents; D000975:Antioxidants; D004396:Coloring Agents; D004273:DNA, Neoplasm; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D007502:Iron Chelating Agents; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; D004281:Docosahexaenoic Acids; C022616:thiazolyl blue