Lock Molecules

Beljanski discovered two plant extracts with anti-cancer activity: Pao  pereira and Rauwolfia vomitoria. The active molecules in the extracts, flavopereirine and alstonine,  bind specifically, or lock on, to the damaged DNA in cancer cells.  The lock molecules disrupt DNA duplication in cancer cells and as a result, the cancer cells are selectively removed from the body.  

 

Beljanski used the Oncotest, one of his most important scientific contributions, to discover the two anti-cancer extracts (1). In the Oncotest, DNA synthesis is set up in test tubes, so the amount of DNA made in different reactions can be compared.  Beljanski compared the total DNA synthesis from normal DNA templates to the total DNA synthesis from cancer DNA templates.  He found that the reactions with cancer DNA templates synthesized more DNA.  He reasoned that this is because the cancer DNA duplex is destabilized, having lost some of the hydrogen bonds that hold the duplex together. So the DNA polymerase works more efficiently and synthesizes more DNA from the destabilized and more accessible cancer DNA template (2). 

 

He understood that an extract that inhibited DNA synthesis from the cancer DNA template while having no effect on the reaction with normal cell DNA would represent an ideal anti-cancer agent. After testing many extracts, he found two, Pao pereira and Rauwolfia vomitoria, that behaved as ideal anti-cancers in the Oncotest.

 

The active compounds, flavopereirine and alstonine, were identified as lock molecules that target the structurally defective cancer DNA and inhibit DNA synthesis in cancer cells (3). Beljanski went on to show and subsequent research has confirmed that the extracts are effective in vivo, against human cancers.  The Oncotest also predicted that the lock molecules would be effective against a broad spectrum of cancers because DNA destabilization is a universal defect of cancer cells (4).  The mechanism revealed in the Oncotest is also at work in vivo: the extracts exert their anti-cancer effect by locking on to the destabilized DNA of cancer cells which initiates apoptosis or cell cycle arrest and selectively destroys cancer cells (5,6).

References

  1. Beljanski, M. “Oncotest: a DNA assay system for the screening of carcinogenic substances“. IRCS Medical science, 1979, 7, pp. 476.
  2. Beljanski, M. et al. “Differential susceptibility of cancer and normal DNA template allows the detection of carcinogens and anticancer drugs. Third NCI-EORTC Symposium on new drugs therapy.” Bordet Institute, Brussels, 1981.
  3. Beljanski, M. & Beljanski, M. S. ““Selective inhibition of in vitro synthesis of cancer DNA by alkaloids of the beta-carboline class.” Exp. Cell Biol, 1982;50(2):79.
  4. Beljanski, M., et al. “Correlation between in vitro DNA synthesis, DNA strand separation and in vivo multiplication of cancer cells.” Exp. Cell Biol., 1981;49(4):220-31.
  5. Bemis,  D., Capodice, J., Gorroochurn, P., Katz, A. and Buttyan. Anti-prostate cancer activity of a ß-carboline alkaloid enriched extract from Rauwolfia vomitoria. International Journal of Oncology. 29: 1065-1073, 2006. https://pubmed.ncbi.nlm.nih.gov/17016636/
  6. Bemis,  D., Capodice, J., Desai, M., Gorroochurn, P., Katz, A. and Buttyan. Beta-Carboline Alkaloid–Enriched Extract from the Amazonian Rain Forest Tree Pao Pereira Suppresses Prostate Cancer Cells. Journal of the Society for Integrative Oncology, Vol 7, No 2 (Spring), 2009: pp 59–65. https://www.researchgate.net/publication/26248012