Scientists are always happy to get a Eureka moment. It was double the delight for a team of researchers at Bangalore’s Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) when they managed two such moments at one go last week.
The JNCASR scientists were trying to unearth the anti-cancer potential of a common anti-hypertensive drug. In the process, they ended up focusing attention on the hitherto unexplored application potential of Raman spectroscopy, a phenomenon named after legendary Indian physicist Sir C.V. Raman who discovered it in the 1920s while working from a two-storeyed building on Bowbazar Street in Calcutta.
The work, published online in the journal Proceedings of National Academy of Sciences, convincingly proved that an advanced technique derived from conventional Raman spectroscopy — called surface-enhanced Raman spectroscopy (SERS) — has the potential to be used for drug discovery.
A powerful tool, Raman spectrometer works by detecting photons, or light particles, scattered when a laser beam is trained on a sample. The instrument actually captures odd photons that exhibit change in energy levels and thus helps analyse the unique chemical signature of the material. The technique has several practical applications in a wide range of fields such as forensics, restoration of old paintings and artefacts and even in medical diagnostics.
“We are happy that we could achieve two major feats with this work,” says molecular biologist Tapas Kundu who, along with fellow JNCASR physicist Chandrabhas Narayana, directed the research.
| Tapas Kundu (top) and Chandrabhas Narayana
Kundu says he is more excited about their exploits with the anti-hypertensive drug felodipine as it has immediate relevance to the common man. “Our studies have shown that felodipine can selectively inhibit an enzyme that is overexpressed in different cancers,” Kundu told KnowHow.
By keeping enzymes belonging to a family of Aurora kinases in rogue cells in check, the biomolecule can actually slow down abnormal cell proliferation and thereby, reduce tumour growth, the lab experiments and animal studies carried out by the JNCASR researchers show.
Kundu says that they were inspired to take up the study of felodipine by the observations of other scientists that patients taking felodipine for their hypertension reduced their risk of developing cancer by 36 per cent. “We wanted to understand what the molecular mechanisms behind this are, if this is true,” he says.
“Felodipine was the frontline drug for treating high blood pressure about a decade ago. Now there are better drugs for hypertension. But it is always exciting to know that a drug is capable of delivering more than what it is supposed to do. At the same time, this research is still in too early a stage to attract a comment,” says Nagaraj Desai, a cardiologist based in Bangalore.
Kundu’s team knew from their previous studies that certain types of Aurora kinases are expressed abundantly in cancers. This prompted them to explore whether felodipine and similar anti-hypertensive drugs acquire their propensity to reduce cancer risk by acting on these enzymes. Establishing this would require the scientists to bind the drug molecule to the enzyme in such a manner that it inhibits the latter’s activity. For this it is important to identify the exact location where the molecule can be docked.
So the JNCASR scientists turned to SERS — an emerging area in Raman spectroscopy — which exploits the potential of gold or silver nanoparticles to amplify the chemical fingerprint of a sample. This technique is capable of capturing even subtle changes that the molecule has undergone, says Narayana.
“As far as we know this is for the first time SERS has been used to understand the drug binding mechanism in a therapeutically important protein, which is an important step in drug discovery,” Narayana told KnowHow.
“What is significant here is that the JNCASR scientists have used this powerful tool (Raman spectroscopy) very effectively to address a genuine scientific problem in drug discovery,” says Ajay Kumar Sood, a physicist at the Indian Institute of Science Bangalore, who specialises in nanotechnology.
SERS has several advantages over X-ray crystallography, a technique which is considered the gold standard for identifying molecular structure of a compound.
Unlike in X-ray crystallography, scientists do not have to make crystals of the protein and the protein-drug complex when they use SERS, says Narayana. The technique could be applied to materials that are in liquid as well as solid form. “The biggest advantage is that studies can be carried out in the protein’s natural environment so that we are sure that the protein is active,” says Narayana.
Besides, SERS requires very little of the sample. “This is very important because we can do these experiments in trace amounts as an elaborate set-up is required to produce therapeutically important proteins in large quantities,” he says.