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Arsenic is a substance whose presence in an environment can lead to cancer development. Some arsenic-based compounds have been used to treat various medical conditions. Arsenic trioxide (ATO) is used for treating cancer. Researchers from the Beth Israel Deaconess Medical Center (BIDMC) in Boston, MA, are investigating the potential of ATO in treating cancer.
Researchers looked at how ATO in combination with another existing drug- trans retinoic acid ATRA can be used for treating promyelocytic leukemia. The researchers worked with models of leukemia, breast, and liver cancer and they were able to find that the ATO-ATRA combination destroyed Pin1 enzyme. Pin1 plays a key role in regulating signaling networks in cancer; it activates over 40 proteins that feed cancer tumors, while also blocking over 20 proteins that would normally suppress tumor growth.
This enzyme is overactive in most types of cancer stem cells, which drive tumor growth and can often be key to cancers’ resistance to traditional treatments. In this study, the scientists discovered that ATO binds to Pin1, blocking its action and eventually leading to the enzyme’s deterioration. At the same time, ATRA which also binds to Pin1 and degrades it, facilitates and increases cells’ uptake of ATO. This leads to the increased expression of a protein specificto cell membranes, which boosts the cells absorption of ATO.
When working with mice engineered not to express Pin1, the researchers also saw that the rodents were actually highly resistant to cancer. These animals suffered no ill effects as a result of the blocked enzyme expression for about half of their lifespans, which suggests that targeting Pin1 at baseline can be a safe approach. Adding [ATO] to existing therapies in treating triple-negative breast cancer and many other cancer types, especially when patients’ cancers are found to be Pin1-positive. This might significantly improve the outcomes of cancer treatment.