Inhibition of 12-O-tetradecanoylphorbol-13-acetate-enhanced transformation in vitro by inhibitors of phospholipid metabolism.
The effects of some inhibitors of phospholipid metabolism were studied using a two-stage transformation assay system in vitro with 3-methylcholanthrene (3-MC) initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion in BALB/3T3 cells. Inhibitors of phospholipid metabolism such as hydrocortisone (HC), p-bromophenacyl bromide (BPB), nordihydroguaiaretic acid (NDGA), quercetin and indomethacin (IM) were used. They were demonstrated to inhibit strongly TPA-promoted transformation. In particular, HC at 1 microgram/ml inhibited the in vitro transformation completely. All the inhibitors used inhibited transformation in a dose-dependent manner. The results suggest that phospholipid metabolism is important for the promotion stage of transformation in BALB/3T3 cells.
Semba
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Laboratory of Cell Toxicology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
Inui
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N
D000818:Animals; D002460:Cell Line / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism; D003043:Cocarcinogenesis; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D006854:Hydrocortisone / Q000494:pharmacology; D008748:Methylcholanthrene / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D010743:Phospholipids / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D010743:Phospholipids; D008748:Methylcholanthrene; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone