Pond Scum Could Be Key to New Cancer Therapies
[Writer] This is research news from U-I-C – the University of Illinois at Chicago.
Today Jimmy Orjala , assistant professor of pharmacognosy at the University of Illinois at Chicago’s College of Pharmacy, talks about discovering new cancer therapies derived from natural sources such as cyanobacteria, or pond scum.
Here’s Professor Orjala:
[Orjala] My research focus is on cyanobacteria – or “pond scrum.” We have received funding from the National Cancer Institute to continue our work with what’s also known as blue-green algae. The collaborative grant is a program grant together with the Ohio State University; the lead investigator is Douglas Kinghorn, who used to be a professor at UIC and is now the Jack L. Beal Professor at Ohio State. We’re also collaborating with Research Triangle Institute in North Carolina, and Bristol-Myers Squibb, as well as Steve Swanson at the UIC College of Pharmacy.
The collaboration is looking for novel anti-cancer agents from natural sources. One focus in our group is cyanobacteria. The focus of the Ohio State group is plants and the RTI group is looking at fungi. So we have a diverse background. And we’re using modern, anti-cancer target assays as well as cell-based assays to evaluate these natural sources for their potential as novel cancer therapies.
The research in my laboratory is focused on cyanobacteria, especially from the Midwest. We collect the samples here in the Midwest. We also have tapped into existing strain collections to expand our diversity. We generally go out, collect pond scum. You may recognize cyanobacteria as the blue-green growth on top of lakes, or the green, slippery things that you step on rocks on a beach. When we see these green, slimy things, that’s where we go. We collect it. We scrape it off. We bring it back to our laboratory and we purify out the pure cyanobacterial strain. At that stage, we can grow it in our laboratory in specific rooms that have temperature and light controls. And out of these strains we grow we can make an extract – we try to get the chemistry out of them by simple extraction. These extracts are then sent out to all our collaborators for biological evaluation in cancer target assays.
Currently we’re focusing on several targets here at UIC. Some of these are modern targets like histone deacetylase and proteasome which are current cancer targets. So far, we’ve had good luck with out hit rate. We have good leads that we’re working on to purify the chemistry out of.
One thing we’ve developed in my laboratory that makes us a bit special is we’ve developed some microanalytical techniques to be able to determine the structure and activity of microgram quantities of metabolites, which helps us to study the cyanobacteria – a very old bacteria. It’s been around for about 3 billion years. It was one of the first to produce oxygen, thus photosynthesis. It’s responsible for changing the atmosphere from reductive to oxidative (giving us) oxygen and it enabled life.
But the thing with this photosynthesis is that it grows fairly slow. So normal, traditional fermentation techniques don’t really work very well. It’s not easy to grow up a liter in 24 hours and be able to study this. Our growth rates are very slow. It takes about 6 to 8 weeks to get 2 liters of fermentation growth, and the biomass yields are very low.
In order for us to study these efficiently, we need to use new techniques, and that’s where our new analytical techniques have come in – especially UIC’s extremely good instrumentation in nuclear magnetic resonance and mass spectrometry enables us to do some of this work on sub-milligram quantities. And since we have the bacteria at hand, any interesting compounds will then be scaled up. Using traditional techniques we can get milligrams, grams of anything we want to, if we want to go into animals or do any further study of any interesting compound.
Our current leads are mainly from the Midwest, but we have also done some collection on the East Coast. We’re also interested in looking at temperate marine organisms, especially from the Pacific Northwest and East Coast. These are areas that are understudied currently. There are not many scientists in these areas looking at it. There are several scientists working with cyanobacteria. Mainly these people are studying them from marine organisms – mostly from tropical marine areas. Many of these studies are being done with wild collected material. Our material is grown in the lab, which gives us a much bigger chance of reproducibility and being able to get more material if we ever need it for any clinical trials or anything like that, which with a wild collection, you may not be able to harvest enough to be able to do that.
So our strength right now is that we have the bacteria and we have right now a collection of about 300 cyanobacterial strains here at UIC, which is a fairly decent-sized collection. All have been grown or are growing. The strains that we’ve grown up and extracted, we have studied. Those strains we store in liquid nitrogen so we have access to all 300 strains any time we need them.
Currently these bioassays that we have been running we have several anti-cancer leads. We have cancer cell lines and in the potential targets our latest hits having both a target and cytotoxicity in a cell line, meaning that we probably know that target already, we now just need to know which structure it is. We know it’s hitting one of the targets and it also shows toxicity in a cell line, so it means that, theoretically, it also penetrates the cell wall which, hopefully, is a more potent lead than some of these others we have.
[Writer] Jimmy Orjala is an assistant professor of pharmacognosy in UIC’s College of Pharmacy.
For more information about this research, go to www-dot-news-dot- uic-dot-edu (www.today.uic.edu) … click on “news releases.” … and look for the release dated July 21, 2008.
This has been research news from U-I-C – the University of Illinois at Chicago.
