In the drive to realize the cancer-fighting potential of magnolia bark extract (MBE) — a remedy long used in traditional Asian medicine for its reported anti-bacterial, anti-inflammatory and digestive health effects — it’s hard to imagine a better research nexus than the Medical College of Wisconsin and Marquette University in Milwaukee.
MCW’s highly regarded Cancer Center is one of several world research sites to observe MBE’s ability to shrink animal tumors. Leading the search for the mechanism at work is Dr. Balaraman Kalyanaraman, MCW professor and chair of biophysics and a foremost expert in the intracellular metabolic processes by which MBE is suspected of weakening and killing tumor tissue.
But that research wouldn’t be complete without the contributions of Dr. Brian Bennett (left), Wehr Distinguished Professor of Physics and physics chair at Marquette, who has both the expertise and technology to help put these theories to the test, using electromagnetic snapshots to reveal MBE’s disruptive effects on mitochondria, the cells’ chief energy source, in the tumor.
Bennett’s special weapon in this anti-cancer fight is an electron paramagnetic resonance spectrometer in the basement of the Wehr Physics Building, originally donated to the university in 2013 and then upgraded significantly through a federal grant secured by Bennett and Dr. Richard Holz, dean of the college. The overhaul took the instrument from analog to digital and added a state-of-the-art cooling system that eliminates the need to spend $2,000 weekly on liquid helium as a cooling agent.
While many research universities have EPR spectrometers, Marquette’s is the only one in the Midwest able to cool samples — at anytime with a flick
of a switch — to a few degrees above absolute zero (minus 273 Celsius), as the process requires. That allows Marquette researchers from physics, chemistry and biology to devote more of their funding to research activity. With previous grant proposals, “the money required for liquid helium ate up a big share of the budget. I could only do a third of the experiments I’d planned to do,” explains Bennett, who also recently used the machine to confirm with MCW researchers that non-titanium hip replacements were leaching muscle- destroying chromium into nearby tissue.
The jagged lines in the image above are revealing spectrometer readings from the mitochondria of oral mice tumors, both untreated (top) and treated (bottom) — with the wider zig-zagging of the lower line indicating a greater presence of destructive free radicals (also known as reactive oxygen species or ROS). “Tumor cells need ROS to a point,” says Bennett.“But tumors are also known to be highly sensitive to these reactive oxygen species. This signal supports the idea that magnolia extract spurs the generation of so much ROS that it poisons the tumor.” Funded by a $40,000 research grant from MCW Cancer Center’s Marquette-MCW initiative, Bennett’s and Kalyanaraman’s findings are providing data to support a much larger inter-institutional program, including proposed trials that will explore MBE’s effects on human tumors along with issues such as the ideal doses of the various active agents in MBE and levels at which those agents might prove toxic to healthy organs and tissue.
“The ROS hypothesis has been tacitly accepted for years and has already informed drug-development efforts, but we hope to be the first to see it rigorously tested to find out whether it provides rational support for ROS-based cancer therapy,” says Bennett.
— By Paula Wheeler and Stephen Filmanowicz