ANTITUMOR EFFECT OF PIERICIDIN B-1 N-OXIDE

Piericidin B-1 N-oxide was isolated from a culture broth of Streptomyc es sp. as a novel inhibitor of phosphatidylinositol (PI) turnover. Pie ricidin B-1 N-oxide specifically inhibited orthophosphate labeling of PI induced by epidermal growth factor (EGF) without affecting the form ation of phosphatidic acid (PA). Like piericidins A(1) and B-1, pieric idin B-1 N-oxide inhibited ATP synthesis in A431 cells; however, the e ffect of piericidin B-1 N-oxide on PI synthesis was stronger than that of piericidins A(1) and B-1. At the concentration inhibiting PI synth esis, piericidin B-1 N-oxide showed no inhibitory effect on DNA, RNA, or protein synthesis. We also demonstrated that piericidin B-1 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 i ntraperitoneal (ip) injection.