Isolation and properties of cytotoxic polyene antibiotics produced by Myxococcus stipitatus JW117

Drug resistance is one of the most significant impediments to successful chemotherapy of cancer. Multidrug-resistance (MDR) is characterized by decreased cellular sensitivity to anticancer agents due to the overexpression of P-glycoprotein. By employing adriamycin-resistance CL02 cancer cells, we undertook the screening for agents which were effective to multidrug-resistant cancer cells. As a result, a myxobacterial strain JW117 was selected for study since the solvent extract of cell mass of the strain was found to exhibit significant activity against the CL02 cancer cells. Cytotoxicity-guided chromatographic fractionation led to the isolation of phenalamides A₁, A₂ and A₃. The producing organism was identified as Myxococcus stipitatus by taxonomic comparison with type strains of Myxococcus sp. as well as its morphological and physiological characteristics. Phenalamides A₁, A₂ and A₃ were as active against drug-resistant cancer cells CL02 and CP70 as against the corresponding sensitive cells with IC₅₀ values ranging from 0.23-0.57 μg/ml.