title: Antitumor effect of piericidin B1 N-oxide.
abstract: Piericidin B1 N-oxide was isolated from a culture broth of Streptomyces sp. as a novel inhibitor of phosphatidylinositol (PI) turnover. Piericidin B1 N-oxide specifically inhibited orthophosphate labeling of PI induced by epidermal growth factor (EGF) without affecting the formation of phosphatidic acid (PA). Like piericidins A1 and B1, piericidin B1 N-oxide inhibited ATP synthesis in A431 cells; however, the effect of piericidin B1 N-oxide on PI synthesis was stronger than that of piericidins A1 and B1. At the concentration inhibiting PI synthesis, piericidin B1 N-oxide showed no inhibitory effect on DNA, RNA, or protein synthesis. We also demonstrated that piericidin B1 N-oxide reversibly inhibited the growth of A431 cells in situ and suppressed the growth of Ehrlich carcinoma in vivo when administered to mice by intraperitoneal (ip) injection.
authors.affiliation: Institute of Microbial Chemistry, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nishioka
authors.forename: M
authors.initials: M
authors.lastname: Imoto
authors.forename: T
authors.initials: T
authors.lastname: Imaoka
authors.forename: T
authors.initials: T
authors.lastname: Sawa
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
authors.forename: K
authors.initials: K
authors.lastname: Umezawa
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000633:toxicity; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology / Q000633:toxicity; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010712:Phosphatidic Acids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D011725:Pyridines / Q000494:pharmacology / Q000633:toxicity; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013302:Streptomyces / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D003497:Cyclic N-Oxides; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D011725:Pyridines; D012334:RNA, Neoplasm; C072163:piericidin B1 N-oxide; D004815:Epidermal Growth Factor; D000255:Adenosine Triphosphate