Products of omega-3 fatty acid metabolism may have anticancer effects
July 13, 2018
Science Daily/University of Illinois at Urbana-Champaign
A class of molecules formed when the body metabolizes omega-3 fatty acids could inhibit cancer's growth and spread, University of Illinois researchers report in a new study in mice. The molecules, called endocannabinoids, are made naturally by the body and have similar properties to cannabinoids found in marijuana -- but without the psychotropic effects.
In mice with tumors of osteosarcoma -- a bone cancer that is notoriously painful and difficult to treat -- endocannabinoids slowed the growth of tumors and blood vessels, inhibited the cancer cells from migrating and caused cancer cell death. The results were published in the Journal of Medicinal Chemistry.
"We have a built-in endocannabinoid system which is anti-inflammatory and pain-reducing. Now we see it is also anti-cancer, stopping the cells from proliferating or migrating," said study leader Aditi Das, a professor of comparative biosciences and an affiliate of biochemistry at Illinois. "These molecules could address multiple problems: cancer, inflammation and pain."
In 2017, the Illinois team identified a new group of omega-3 fatty-acid metabolites called endocannabinoid epoxides, or EDP-EAs. They found that these molecules had anti-inflammatory properties and targeted the same receptor in the body that cannabis does.
Since cannabis has been shown to have some anti-cancer properties, in the new study the researchers investigated whether EDP-EAs also affect cancer cells. They found that in mice with osteosarcoma tumors that metastasized to their lungs, there was an 80 percent increase in naturally occurring EDP-EAs in cancerous lung tissues over the lungs of healthy mice.
"The dramatic increase indicated that these molecules were doing something to the cancer -- but we didn't know if it was harmful or good," Das said. "We asked, are they trying to stop the cancer, or facilitating it? So we studied the individual properties and saw that they are working against the cancer in several ways."
The researchers found that in higher concentrations, EDP-EAs did kill cancer cells, but not as effectively as other chemotherapeutic drugs on the market. However, the compounds also combated the osteosarcoma in other ways: They slowed tumor growth by inhibiting new blood vessels from forming to supply the tumor with nutrients, they prevented interactions between the cells, and most significantly, they appeared to stop cancerous cells from migrating.
"The major cause of death from cancer is driven by the spread of tumor cells, which requires migration of cells," said study coauthor Timothy Fan, a professor of veterinary clinical medicine and veterinary oncology. "As such, therapies that have the potential to impede cell migration also could be useful for slowing down or inhibiting metastases."
The researchers isolated the most potent of the molecules and are working to develop derivatives that bind better to the cannabinoid receptor, which is plentiful on the surface on cancer cells.
"Dietary consumption of omega-3 fatty acids can lead to the formation of these substances in the body and may have some beneficial effects. However, if you have cancer, you want something concentrated and fast acting," Das said. "That's where the endocannabinoid epoxide derivatives come into play -- you could make a concentrated dose of the exact compound that's most effective against the cancer. You could also mix this with other drugs such as chemotherapies."
Next, the researchers plan to perform preclinical studies in dogs, since dogs develop osteosarcoma spontaneously, similarly to humans. They also plan to study the effects of EDP-EAs derived from omega-3 fatty acids in other cancer types.
"Particular cancers that might be most interesting to study would be solid tumors or carcinomas, which tend to spread and cause pain within the skeleton. Some of the most common tumors that behave this way are breast, prostate, and lung carcinomas, and we can certainly explore these tumors in the future," said Fan, who is also a member of the Carle Illinois College of Medicine, the Cancer Center at Illinois and the Carl R. Woese Institute for Genomic Biology.
https://www.sciencedaily.com/releases/2018/07/180713220137.htm
Cannabinoid compounds may inhibit growth of colon cancer cells
February 6, 2019
Science Daily/Penn State
Medical marijuana has gained attention in recent years for its potential to relieve pain and short-term anxiety and depression. Now, Penn State College of Medicine researchers say some cannabinoid compounds may actually inhibit the growth of colon cancer cells in the lab.
The researchers tested the effects of synthetic cannabinoid compounds on colon cancer cells in an experiment in test tubes. While the compounds most commonly associated with cannabis -- THC and CBD -- showed little to no effect, 10 other compounds were effective at inhibiting cancer cell growth.
Kent Vrana, chair of the Department of Pharmacology at Penn State College of Medicine, said the study -- recently published in Cannabis and Cannabinoid Research -- helped identify compounds that could be tested further to understand their anti-cancer properties.
"Now that we've identified the compounds that we think have this activity, we can take these compounds and start trying to alter them to make them more potent against cancer cells," Vrana said. "And then eventually, we can explore the potential for using these compounds to develop drugs for treating cancer."
Colorectal cancer is one of the most common cancers diagnosed in the United States, according to the National Cancer Institute, with an estimated 140,250 newly diagnosed cases and 50,630 deaths in 2018. While medical cannabis has largely been used in recent years for palliative care, the researchers said some previous studies suggested that certain cannabinoid compounds may have the potential to inhibit or prevent the growth of tumors.
To explore how effective cannabinoids were at reducing the viability of colon cancer cells specifically, the researchers tested how 370 different synthetic cannabinoid compounds affected seven types of human colon cancer cells.
"There are many different ways cells can become cancerous," Vrana said. "Each of the seven cells we tested had a different cause or mutation that led to the cancer, even though they were all colon cells. We didn't want to test these compounds on just one mutation or pathway to cancer."
The researchers incubated the cancer cells in a lab for eight hours before treating them with the cannabinoid compounds for 48 hours. Any compounds that showed signs of reducing the viability of one kind of cancer cell was then used to treat all seven kinds of cells.
After further screening and analysis, the researchers identified 10 compounds that inhibited the growth of almost all seven types of colon cancer types tested. But while the researchers were able to identify these compounds, Vrana said they are still unsure about how exactly the compounds worked to reduce the viability of the cancer cells.
"The 10 compounds we found to be effective fall into three classes, so they're similar to each other but with small changes," Vrana said. "We know how one of them works, which is by inhibiting the division of cells in general. We also found that the most potent and effective compounds don't seem to work through traditional marijuana receptors, although we're not sure of the exact mechanism yet."
Vrana said certain types of cells, like skin and colon cells, are more susceptible to cancers because they divide very frequently: "Every time a cell divides, there's the chance that it will mutate and keep dividing when it shouldn't, which is how cancers can start. So if we block that signal that's telling cancer cells to continue to divide, that could be a way to stop that cancer."
Vrana said that because the other compounds did not seem to be working through traditional cannabinoid signaling pathways, future research will focus on better understanding how the compounds interact with cancer cells and whether researchers can make the compounds more potent and effective.
https://www.sciencedaily.com/releases/2019/02/190206091420.htm