A major problem in treatment of cancer is multi-drug-resistance (MDR,) which can be natural to the tumor cells or can develop during the course of chemotherapy. Some cancer cells are or become resistant to many chemicals which are used to treat the cancers.
Chemicals called cardiotonic steroids (including cardenolides and bufadenolides) bind the cell wall Na+/K+-ATPase enzyme. These chemicals act at the extremely low nMol. (nanomolar) levels. They prevent cancer cell multiplication.
A partially synthetic cardenolide, 19-hydroxy-2″oxovoruscharin, is active in relieving MDR, even when it is caused by very strong chemotherapeutic agents. The chemical reduces ATP levels in cancer cells, but, not in normal cells. (MDR cells have very high ATP energy needs and cannot survive without ATP.) This cardenolide is derived from the root bark of a plant from Africa, Calotropis procera. No cancer cells have been found that are resistant to this chemical. Tumors can’t become resistant to this synthetic agent even if they are “notoriously resistant cancers.”
The cardiotonic steroids, ouabain and digoxin, inhibit Na+/K+-ATPase, but, they “upregulate” MDR related genes. This reduces their effectiveness against cancer. 19-hydroxy-2″oxovoruscharin does not “upregulate” MDR genes, making it more effective against cancer. Some cardiotonic steroids can even induce MDR.
CONCLUSION: Blocking Na+/K+-ATPase activity in cancer cells is new in anticancer treatment. A partly synthetic cardiotonic steroid, 19-hydroxy-2″oxovoruscharin, is very effective in reducing MDR in cancer cells when chemotherapy fails because of MDR.
NOTE: Multi-drug-resistance (MDR) is the ability of cells to resist the usual drugs, such as antibiotics or chemotherapeutic agents, used to treat infections or cancer. ATPase is an enzyme which plays a role in MDR. Read about the ability of quercetin to reverse multi-drug resistance.
ATP (adenosine-5-triphosphate) is a carrier of energy.
Nanomolar is a very low unit of measure of how much of a material is in a solution. Nanomolar is the level at which chemicals can alter DNA and RNA.
To read the author’s abstract of the article click on the link to the author’s title of the article above.
PMID: 19339106.
Summary #444.
