There is considerable interest in developing new chemotherapy drugs that are effective against cancer without causing side-effects. Cisplatin is an FDA-approved platinum drug that causes side effects including hearing loss.
New research published by WKU researchers in PLOS (Public Library of Science)’s journal, PLOS ONE, showed that a set of structurally unique platinum compounds are effective against cancer but do not damage sensory hair cells that are responsible for hearing and are typically harmed by conventional platinum chemotherapy compounds.
Researchers from WKU’s Biology and Chemistry departments worked together to see how several novel platinum compounds affected cancer and auditory hair cells. These new compounds bind to DNA differently than FDA-approved platinum chemotherapy compounds like cisplatin, and this could allow them to kill cancer cells without damaging the sensory hair cells used for hearing.
Dr. Kevin Williams (Chemistry) and his students synthesized the platinum compounds and measured their DNA binding efficiency. They then used atomic absorption spectroscopy to determine how efficiently the compounds entered the cells and targeted the nucleus in several cancer cell lines.
Dr. Michael Smith and his researchers then measured the effect of the compounds on cancer cell viability. Compounds that were effective against cancer cells were then injected into zebrafish, which have auditory hair cells similar to those found in humans. The zebrafish were then given hearing tests, and their auditory hair cells were microscopically examined for signs of damage.
The authors of this study believe that it could lead to the development of new chemotherapy drugs that can kill cancer without producing auditory and other side-effects associated with traditional platinum-based chemotherapy. Future investigations will consider how these chemicals effect gene transcription and whether any hearing loss they produce is temporary.
The research team is also now investigating additional platinum compounds with novel structural features and intend to examine their effects on cancer and hearing. This research was supported by the Kentucky Science and Engineering Foundation (14850214325) and the National Institutes of Health (R15 CA188890-01A1, P20 GM103436-14, P20 GM103436-16).
Contact: Dr. Michael Smith, (270) 745-2405