Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Na/K-ATPase, endogenous digitalis like compounds and cancer development - a hypothesis
The primary transport system of sodium and potassium across the plasma cell membrane, the Na/K-ATPase, is a vital enzyme involved in numerous cellular events. This enzyme is the receptor for plant and amphibian steroids such as ouabain, digoxin and bufalin. In the past decade several endogenous steroids, identical or similar to the plant and amphibian steroids, termed here collectively digitalis-like compounds (DLC), have been identified in human tissues. This paper raises the hypothesis that alterations in the metabolism of endogenous DLC and in their interactions with the Na/K-ATPase may be associated with the development of malignancies. This hypothesis is based on the review of the literature pointing to: 1. An abnormal activity of the Na/K-ATPase and its sensitivity to DLC in malignant cells; 2. Abnormal plasma DLC concentrations in cancer patients; 3. Abnormal synthesis and release of DLC in immune compromised mice; and 4. Beneficial effects of DLC in the treatment of cancer.