Novel anticancer agent, benzyldihydroxyoctenone, isolated from Streptomyces sp. causes G1cell cycle arrest and induces apoptosis of HeLa cells

摘要: In the course of screening for anticancer agents, a novel active compound, F3-2-5, was isolated from culture broth Streptomyces sp., KACC91015. Its structure identified using nuclear magnetic resonance, mass spectrometry, and molecular modeling experiments, confirmed by total synthesis. The growth various human cancer cell lines inhibited in dose-dependent manner 0.06-0.48 mM F3-2-5 over 24 h. IC(50) values were estimated at 37 microM on HeLa, 72 A549, 190 HT-29 cells. However, had no antiproliferative effect normal lymphocytes fibroblasts used as controls. Moreover, it affected cycle regulation caused apoptosis HeLa cells; chromatin condensation DNA fragmentation observed cells exposed to 80 F3-2-5. Western blot analysis revealed that phosphorylation retinoblastoma protein (pRb) reduced expression cyclin-dependent kinase-4 -6, cyclin D1 E, while levels p53 p21(WAF1/CIP1) increased. Taken together, these findings show inhibits proliferation inducing G(1) phase arrest consequence inhibition pRb following up-regulation p53. Furthermore, treated with associated an increase Bax p53, leading release cytochrome c, activation caspase-3, -8, cleavage poly (ADP-ribose) polymerase.