New research by a team at the Indian Institute of Technology-Madras suggests that doctors may be able to improve the outcome of cancer therapy by merely changing the time of administering drugs.
The basis
This work is rooted in the rhythms of reactive-species production. This is how it works. In the course of day-to-day life, all life forms produce highly reactive molecules called reactive-species. Small doses of these molecules can aid biological functions. But when produced at high rates, they can also kill the cell by creating oxidative stress. Most cancer drugs seek to kill malignant cells by producing rapid bursts of reactive-species. Because there is a lack of specific action, the drugs also end up affecting normal cells surrounding cancerous tumours.
Variation in internal reactive-species production has been a neglected area of research. The research team, led by G.K. Suraish Kumar, found a lot of fluctuation in levels of reactive-species within a cell. These short-term fluctuations can be ignored when studying much slower processes (such as cell growth) and researchers work with average levels instead.
As cancer therapy relies on increasing the oxidative stress beyond a critical point, the timing of internal rhythms in reactive-species production is crucial. The scientists found that two important reactive-species used for targeting cancer cells (superoxide radicals and hydroxyl radicals) peak at an interval of 15.4 hours and 25 hours, respectively.
They reasoned that by aligning drug administration with internal rhythms of reactive-species production, the efficiency of drugs could be increased. In order to test this hypothesis, they administered two drugs, menadione and curcumin, to cervical cancer cell lines and a colon cancer cell line.
The results
By just changing the timing of drug administration, the researchers could reprogramme internal rhythms of reactive-species production. For instance, treating cancer cells with curcumin at the time of increased superoxide production ensured that the superoxide radical would peak after every nine hours. By tuning drug dose to hydroxyl-radical production, the periodicity of its rhythm was reduced from 25 hours to 11 hours. This, in turn, improved the drug’s efficiency by 20%.
The strategy is non-invasive and can be extended to any cancer drug that operates via the production of reactive-species. The researchers are now planning to extend this to patients. “All we will have to do is change the timing of treatment in tune with the peaking of reactive-species production,” explains Prof. Suraish Kumar. “We believe that doing so will also reduce the complications associated with cancer treatment.”
Others in the research team include Karunagaran, Raghunathan Rengaswamy, Uma Kizhuveetil, Meghana Palukuri, Prerna Bhalla and Steffi Jose. The research project has been financially supported by the Science and Engineering Research Board of the Department of Science and Technology.
— India Science Wire
