Combined, two small molecules inhibit prostate cancer cell proliferation

May 1, 2019
Beth Zucconi published the research in the March 2019 issue of Biochemistry.


Two small molecules can synergistically inhibit prostate cancer cell proliferation, according to recent research published in Biochemistry by Beth Zucconi.

The research focuses on p300, an enzyme that regulates cell growth, differentiation, and gene expression in many pathways across many organ systems. When its function is disrupted — by mutation, a change in its expression, or any other alteration — disease can result. In many cancers, p300 is overactive.

Zucconi’s study found that, together, two small molecules can lower the presence of the enzyme p300 on chromatin, which reduces the expression of mRNAs of prostate cancer genes and therefore inhibits prostate cancer proliferation.

In the future, these molecules, A485 and I-CBP112 could provide the basis for therapeutic drugs. “A485 has more current therapeutic promise and has been used in mice,” says Zucconi, who was a JCC Fellow from 2014 to 2017 with Philip Cole first at Johns Hopkins University School of Medicine and then at Harvard. “But I-CBP112 might be able to be modified to make it more bioavailable.”

Zucconi also recently contributed to another study, published in Cancer Research, that identified a therapeutic target of melanoma. The study found that cells expressing a specific transcription factor (MITF) are particularly sensitive to A485 inhibition of p300 activity. This suggests that the presence of MITF can help predict the success of treatment with p300 inhibitors.