In cachectic mouse tumor models (PC-3 human prostate cancer, T47 human breast cancer, HL-60 human leukemia, HT-168 human melanoma), a selected relatively non-toxic compound, ZKC1, greatly reduced the loss of body weight (see Table below) and reduced loss of muscle proteins by 60-70% when daily subcutaneous treatment started soon after tumor transplantation on day 17 lasting until day 27. These effects were associated with increased survival. In non-cachectic tumor models (for example, rodent MTX breast cancer or rodent B16 melanoma) ZKC1 had no significant effects on body weight and muscle proteins.
Directions of Research
1.In vitro experiments suggest that one component of the ZKC1 effect on muscle proteins may involve inhibition of myostatin, a known regulator of muscle protein synthesis. This avenue of research using relevant mouse models is further pursued.
2. Increased total content of choline-containing compounds is a characteristic of cancer cells which is associated with both malignant progression and cachexia. The company’s research so far has revealed that while ZKC1 enhanced choline transport and its subsequent metabolism in normal cells, it inhibited the same processes in cancer cells (that express different choline transporters) derived from cachectic tumors. This research will continue.
3. The most effective and least toxic ZKC compound from our long list will be identified.