Antitumor efficacy in vitro and in vivo of falconensones, a new type of polyene

Falconensones A and B are new type of yellow pigment isolated from the myce lial extract of ascomycetous fungi, Emericella falconensis. To date, these falconensones and their derivatives, falconensone A p-bromophenylhydrazone and falconensone A dioxime are known to exhibit biological activities, whic h include growth inhibition and both induction of differentiation and apopt osis of HL60 human leukemia cells. The synthetic derivatives have been show n to be more potent than natural falconensone A and B in eliciting these ac tivities. Herein, we investigate whether falconensones inhibit growth of ot her cancer cell lines in vitro, and we evaluate their ability to modify sur vival in C57 BL/6J mice using M5076 murine reticulosarcoma in vivo, which i s established as the metastasis model. Falconensone A, falconensone A p-bro mophenylhydrazone, and falconensone A dioxime inhibit growth of human myelo id leukemia cell lines, IHL60 and HL60R, human hepatoma cell line HepG2, hu man prostate cancer cell line DU-145, and human breast cancer cell line MCF -7/Adr(R), whereas falconensone B, the 4'-nor-methyl derivative of falconen sone A, shows extremely low or no activity. In contrast, all of the falcone nsones are active in growth inhibition of human breast cancer cell line MCF -7. Survival time of M5076-implanted mice was prolonged by treatment with f alconensones, particularly falconensone A dioxime. These results indicate t hat falconensone A and its derivatives exhibit anticancer efficacy in a bro ad spectrum of cancer cell lines. These agents may have great potential for clinical use in the treatment of various cancers.