This colorless odorless gas safely destroys cancer
Carbon monoxide (CO) that is naturally in the environment and a byproduct of automobile combustion is highly toxic. But scientists say the gas helps destroy cancer and protects healthy cells at the same time, given in low doses that are safe. The surprising finding that is published in the December issue of the journal Cancer Research revealed carbon monoxide boosts the effect of chemotherapy 1,000-fold; discovered in cell cultures and then in animal models.
The gas also stopped the growth of prostate and lung cancer tumors while sparing healthy cells and tissue. Carbon monoxide also made the chemotherapy drugs doxorubicin and camptothecin more toxic to cancer cells, given in small, controlled doses.
Leo Otterbein, PhD, an investigator in the Transplant Institute in the Beth Israel Deaconess Medical Center (BIDMC) Department of Surgery and Associate Professor of Surgery at Harvard Medical School explained in a press release the gas not only spares healthy tissue but protects normal tissue from the toxic effects of chemotherapy.
The researchers explain carbon monoxide changes cancer tumor’s metabolism to lead to destruction.
Otterbein explains: “Cancer cells are able to alter their metabolism in processing sugars and other energy sources, which enable them to rapidly proliferate and spread. This shift in metabolism is known as the Warburg Effect. Our findings indicate that CO essentially induces an ‘anti-Warburg’ effect, rapidly fueling cancer cell bioenergetics by compelling the cancer cell to increase respiration, which ultimately results in metabolic exhaustion.”
Otterbein and first author Barbara Wegiel, PhD, also an investigator in BIDMC’s Transplant Institute specifically wanted to find out if absence of carbon monoxide in tumors fuels growth.
Cancer cells, unlike normal cells, generate low levels of carbon monoxide that is naturally produced in the body from stressors such as trauma, inflammation and tissue repair through the expression of the gene heme oxygenase-1 (HO-1Hmox1). Cancer cells lack the ability to express the gene that generates CO.
“If A plus B equals C, then, we reasoned, if you administered carbon monoxide to tumors, you would reestablish a tumor cell’s ability to regulate its cell growth, and so, too, slow that growth,” says Otterbein in a press release.
For their investigation the researchers first confirmed the absence of CO in prostate tumor cells by analyzing more than 500 prostate cancer tumors obtained from biopsies.
Wegiel explained though HO-1 was present in the tumors, it “…was simply not active. It was not producing sufficient amounts of CO, and we thought this was contributing to altered cell growth and malignancy.”
The researchers then surmised HO-1’s ability to produce CO might be regulating cancer growth.
To test their hypothesis the researchers gave mice with cancer tumors low amounts of inhaled carbon monoxide for one hour a day in safe amounts.
The team measured the size of the mouse tumors over a period of four to six weeks.
They discovered prostate cancer cells became more sensitive to chemotherapy. The tumors activity changed with carbon monoxide given at doses already approved for humans in clinical trials.
“CO targeted mitochondria activity in cancer cells as evidenced by higher oxygen consumption, free radical generation and, ultimately, mitochondrial collapse,” Otterbein said.
Most importantly the researcher said is there was no adverse effect on normal cells. The effect of carbon monoxide protected healthy cells from DNA damage that can come from cytotoxic chemotherapy agents.
Otterbein explains normal cells went into a state of hibernation; consuming less oxygen. In contrast, cancer cells continued to take up oxygen which ultimately lead to their death.
Study coauthor and BIDMC Chief Academic Officer Vikas Sukhatme, MD, PhD says carbon monoxide treatment could potentially make chemotherapy drugs more effective, less toxic and with fewer “terrible” side effects.
“There are ongoing innovative methodologies being designed and tested to deliver CO directly to the tumor site, which might obviate the need for additional drugs. Indeed, small molecules are being designed that can carry CO as a cargo and deliver it in a tissue-specific manner,” Sukhatme says.
The study suggests a future role for carbon monoxide as a cancer treatment, though more studies are needed to confirm the findings.
Image credit: Wikimedia Commons