Dithiazanine iodide is an antiparasitic compound that has anticancer properties in vitro and is associated with decreased mitochondrial electron transport protein expression, as well as cellular ATP depletion in cholangiocarcinoma cells, according to a poster being presented at the NORD Breakthrough Summit 2021.
These results support the potential use of the compound as a therapy for the disease.
Cholangiocarcinoma is a type of cancer that is highly resistant to standard chemotherapy, and mitochondrial inhibition has emerged as a potential new approach to treat the disease.
In this study, a team of researchers was led by Avinoma Nevler, MD, from Thomas Jefferson University in Philadelphia, Pennsylvania. They assessed the potential of dithiazanine iodide as an anticancer drug in 2 cholangiocarcinoma cell lines grown in culture.
Read more about cholangiocarcinoma therapies
They found that the cell lines were markedly more sensitive to dithiazanine iodide than to the chemotherapeutic agents 5-fluorouracil and irinotecan.
Moreover, while ATP levels remained normal in nontreated cells and cells treated with chemotherapy drugs, they decreased when cells were treated with known mitochondrial inhibitors and dithiazanine iodide.
Finally, the researchers showed that there was a marked decrease in mitochondrial electron transport protein expression in cholangiocarcinoma cells treated with dithiazanine iodide. This led them to conclude that the cause of mitochondrial inhibition is a decrease in mitochondrial gene expression or increased mitochondrial electron transport protein degradation.
Mitochondria are known to play a key role in oncogenesis due to the high energy demands of rapidly growing and spreading cancer cells. Mitochondrial inhibition, therefore, holds great potential as an anticancer strategy.
The US Food and Drug Administration (FDA) approved dithiazanine iodide as an animal drug product. It is used as an anthelmintic to treat dogs and can be lethal for humans at a dose of 4 to 16 mg per kg by oral ingestion.
Targeting cellular metabolism in cholangiocarcinoma using repurposed novel mitochondrial inhibitors. Poster presented at: NORD Breakthrough Summit 2021: October 18-19, 2021; Virtual.