Flavone-8-acetic acid augments systemic natural killer cell activity and synergizes with IL-2 for treatment of murine renal cancer

The investigational drug flavone-8-acetic acid (FAA) potently augments NK activity in the spleen, liver, lungs, and peritoneum in a dose-dependent manner after i.v. or i.p. administration. Augmented NK activity peaks by 24 h after FAA injection and returns to normal after 6 days. Combined treatment of established murine renal cancer with FAA and rIL-2 results in up to 80% long term survival whereas FAA or rIL-2 alone were unable to induce any long term survivors. The optimal dose of rIL-2 required for use with FAA was in the range of 10,000 to 30,000 U/day. Further studies demonstrated that the regimen of FAA plus rIL-2 administration that was effective in treating established murine renal cancer also induced a more potent augmentation of NK activity than did either FAA or rIL-2 alone. Subsequent studies revealed that the therapeutic effectiveness of FAA plus rIL-2 was significantly reduced when tumor-bearing mice were treated with anti-asialo GM1 serum. These results are consistent with a role for augmented NK activity in the therapeutic effects of FAA plus rIL-2 murine renal cancer. In addition, these studies demonstrate that FAA and rIL-2 is a useful approach for cancer treatment in that subtoxic doses of rIL-2 can be used and significant anti-tumor efficacy occurs even without accompanying adoptive immunotherapy.     

The functioning of cytochrome b in the electron transport to fumarate in Propionibacterium freudenreichii and Propionibacterium pentosaceum

Fumarase-free electron particles from Propionibacterium freudenreichii and P. pentosaceum were prepared by discontinuous sucrose gradient centrifugation, and the influence of 2-n-heptyl-4-hydroxy-quinoline-N-oxide (HQNO) and ultraviolet irradiation on the reduction of menaquinone and cytochrome b with l-lactate or glycerol-3-phosphate and the reoxidation by fumarate was studied. In the presence of HQNO the steady state reduction level of menaquinone during fumarate reduction was increased whereas the steady state reduction level of cytochrome b was decreased as compared with the reduction levels measured in the absence of HQNO. The steady state reduction level of menaquinone during electron transport to fumarate was not influenced by ultraviolet irradiation and the steady state reduction level of cytochrome b was decreased at increasing irradiation times. The data indicate that cytochrome b is involved in the electron transport to fumarate.Abbreviations HQNO 2-n-heptyl-4-hydroxyquinoline-N-oxide - NQNO 2-n-nonyl-4-hydroxyquinoline-N-oxide Visiting Professor at the Biological Laboratory