Antitumor effect of piericidin B₁ N-oxide

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.