New research has placed its focus on a diet high in fat, i.e. dietary fat and nitric oxide (NO), the high levels of which have been linked to the development of inflammation, and inflammation, in turn, has been linked to incidence of neoplasms.
The results of the study have been published in the scientific journal ACS Central Science.
High-fat diet and cancer: this is what the research says
To study nitric oxide (NO) at the molecular level, a research team from Chan Lab at the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign (UIUC) developed a molecular probe capable of producing images deep inside the body tissue. Dubbed BL660-NO, the spacecraft gave researchers a glimpse into tumor microenvironments.
The researchers visually confirmed higher NO levels in mice fed a high-fat diet compared to mice on a low-fat diet.
Research co-author Dr Anuj Yadav said: “They are trying to understand how subtle changes in the tumor microenvironment affect cancer progression at the molecular level.”
A molecular probe is a group of atoms or molecules that is used to analyze the properties of other molecules by examining the interactions between the probe and the molecules of interest. BL660-NO is a NIR (near infrared) bioluminescent probe. While other molecular activity-based detection (ABS) probes have been developed, BL660-NO is the first specifically developed for NO imaging.
Professor Jefferson Chan, associate professor of chemistry at UIUC and principal investigator of the cancer-related high-fat diet study, said, “Our group specializes in creating designer molecules, which allow us to observe the molecular characteristics that they are invisible to the naked eye. We design these bespoke molecules to discover things that weren’t known before. “
Dr. Douglas D. Thomas, an associate professor in the Department of Pharmaceutical Sciences at the University of Illinois, Chicago, who was not involved in the study, added: “They have developed a tool potentially useful to measure NO levels in vivo, which is not easy to do. This tool can accelerate the pace of research into NO-associated diseases, including cancers“.
The bioluminescence imaging-based probe will be extremely useful for detecting NO in a tumor microenvironment, ”said Dr. Deepak Nagrath, an associate professor of biomedical engineering at the University of Michigan, who was not involved in the study. : “In particular, based on the recent interest in understanding the synergistic role of diet and chemotherapy, this probe will shed light on the dynamics and heterogeneity that exist in tumors.”
The group of experts carried out research on diet using mice BALB / c bearers of breast cancer. Mice that ate a high-fat diet where 60% of the calories came from fat became obese and developed large tumors. Experts gave the control group a 10% fat diet and found nitric oxide levels in both groups.
The researchers also observed an increase in nitric oxide in mice fed a high-fat diet.
“The implication of this is that the tumor microenvironment is a very complex system and we really need to understand it to understand how cancer progression works,” explained study co-author Michael Lee, researcher at Chan Lab: “Many factors can go into this, from diet to exercise, external factors that we don’t really take into account that we should when considering cancer treatments.”
“These are potentially interesting results. However, this is a study in mice, and based on their results, I don’t think a mechanistic causal link can be established between a high-fat diet, NO amounts detected and a worse result without further experimentation, ”noted Dr. Tomas.
Although the study supports the idea that nitric oxide is needed in a tumor microenvironment, high doses of it are also used in chemotherapy as a means of killing cancer cells. This shows that the link between nitric oxide and cancer is complex. Dr Nagrath explained that nitric oxide acted in a “bimodal way” in the cancer cells: ““A low concentration of NO supports tumor growth, proliferation and metastasis, while a high concentration kills cancer cells through DNA damage and nitrosative stress. This dual role of NO could also depend on the diet and the tumor microenvironment “.
“In some cases, the presence of NO (or the enzymes that produce NO) correlates with a better patient prognosis, but more often NO is associated with more aggressive tumors. There are also some experimental cancer therapies designed to deliver NO to a tumor, ”Tomas said.
Professor Chan said that thanks to this technology, they were able to locate this missing molecular link: “Now that we know this is happening, how can we prevent it and how we can improve the situation” concluded the expert.
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