expressing NFAT3c-GFP
A little-studied chemical compound has “wide and potent” anticancer activity, investigators have reported in Cancer Cell.
The compound, BMH-21, works by inhibiting the RNA polymerase transcription pathway (Pol I), thereby preventing cancer cell communication and replication.
“Without this transcription machinery, cancer cells cannot function,” said study author Marikki Laiho, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.
She and her colleagues homed in on BMH-21 by screening a library of chemical compounds thought to have potential for anticancer activity.
Specifically, the team looked at the compounds’ ability to interfere with transcription in the National Cancer Institute’s collection of 60 human tumor cell lines (known as NCI-60).
BMH-21 demonstrated activity against all 9 cancer types studied—leukemia and melanoma, as well as breast, CNS, colon, lung, ovarian, prostate, and renal cancers.
The drug also repressed tumor growth in mouse models of colon cancer and melanoma.
Additional analyses showed that BMH-21 inhibited Pol I transcription and caused disintegration of the nucleolus. The drug activated loss of the Pol I catalytic subunit RPA194, which led to disassembly of the Pol I holocomplex from the ribosomal DNA.
And the loss of RPA194, which was a result of increased proteasome-mediated turnover, was associated with decreased cancer cell viability.
Dr Laiho and her colleagues are continuing studies of BMH-21 in animal models to confirm the drug’s anticancer activity, identify any toxicities associated with the compound, and determine the optimal dose.
And because Pol I activity is frequently deregulated in cancers, the investigators believe BMH-21 could have therapeutic potential for many malignancies.
Dr Laiho is currently collaborating with experts in multiple myeloma, medullary thyroid cancer, and prostate cancer to explore the drug’s activity in these malignancies.
