October 27, 2014
Could Selenium be the newest weapon in the battle against breast cancer?
Julian Spallholz has an old black and white picture above his desk. It looks like a collection of red blood cells, yet they all seem off. Instead of the pretty, smooth, disc shapes normally seen under a microscope, the cells have jagged edges, non-symmetrical shapes and look broken. It's a frightening image.
Now imagine those broken cells are breast cancer, and suddenly the picture looks much rosier.
Spallholz, a nutritional sciences professor in Texas Tech University's College of Human Sciences, researches the effect of selenium, element No. 34 in the periodic table that is an essential nutrient in small doses and a killer in larger doses. He's looked at prostate cancer, leukemia and HER2 positive breast cancer and, so far, can say with some confidence selenium destroys cancer cells and does so more quickly by modification of the existing cancer antibody treatments on the market today.
The research is still in its early phases; it has only been tested in a lab, not on people or even animals. So far all tests performed on cells show dramatic results.
“I think what would happen is that with the selenium attached and some more experimentation, you could administer this antibody in the same way that you do today, but you could do so in a lower antibody dose,” he said. “I think it will be a much better treatment than the existing treatments that are commercially available.”
Where did this start?
Spallholz has worked with selenium since he was a graduate student at Colorado State University in the 1960s, but not until 1991 did he find a way that selenium, when attached to a molecule needed by a cancer cell for growth, could inhibit cancer. He has since attached selenium both to commercial antibodies that specifically target cancer and folic acid, which cancer cells suck up at higher rates than normal cells because it aids in growth.
Spallholz's research uses both commercial antibodies and folic acid as a sort of Trojan horse for cancer cells. He attaches selenium to antibodies or folic acid and delivers it into a Petri dish, where the cancer cells grab them. The selenium, now inside the cancer cell, destroys the cell, doing what he calls “funny chemistry,” generating free radicals and destroying only the cancer cell from within.
Cancer Cells Treated with Equal Amounts of Herceptin and Se-Herceptin. The blue stain
indicates dead or dying cells.
Click to enlarge.
What is HER2 positive breast cancer?
Human epidermal growth factor receptor (HER) 2 promotes cell growth, including cancer cells. In HER2 positive breast cancer, the cancer cells overexpress HER2, which allows the cancer to grow more rapidly. According to the Mayo Clinic, this type of breast cancer is more aggressive than other breast cancers and less responsive to hormone treatments.
About 20 percent of all breast cancer cases are considered HER2 positive.
What is the current treatment method?
According to the manufacturer, Herceptin works by targeting breast cancer cells that are overexpressing the HER2 receptors. It latches onto the HER2 receptors and inhibits the signal from the receptor that tells the cell to divide while also sending a signal to immune cells that the cancer cell needs to be destroyed. This is an effective means of destroying the cancer, but both it and another treatment, called Tykerb, carry the potential risk of congestive heart failure.
Herceptin, by far the most common treatment for HER2 positive breast cancer, has another problem: doctors have found the cancer can adapt to this treatment. Spallholz's research has been conducted on some of these drug-resistant cells, which were developed from a 62-year-old Finnish woman.
Cancer Cells; Detection of Superoxide inside Cancer Cells with Fluorecense dye. The
stronger red color means more superoxide generation, all cells generate superoxide;
the Se-Herceptin is excellerting the internal generation of superoxide.
Click to enlarge.
“After a year or so of treatment, for many women, the cancer becomes resistant,” he said. “That's why you get recurrences.”
Genentech, the same company that produces Herceptin, had a similar idea to Spallholz; a new antibody product, Kadcyla, combines the targeting ability of Herceptin with an attached cytotoxic drug, which is supposed to kill the cancer cells.
How does the selenium work?
Spallholz and his doctoral student, Priyanka Bapat, attached selenium to a Herceptin molecule and sent it after Herceptin-resistant breast cancer cells. Bapat said they found the Herceptin still targets the cell and the selenium kills it.
Spallholz pointed to graphs comparing the effect of Herceptin and different levels of selenium on the Herceptin-resistant cancer cells. Each test showed roughly the same results: Selenium killed cancer cells more quickly than Herceptin alone or Kadcyla. Bapat said the Herceptin-resistant cancer cells had a higher sensitivity to selenium.
“Selenium attached to Herceptin is killing cells more quickly and at lower concentration,” Spallholz said.
What does this mean for cancer patients?
Comparison of Treated Herceptin Resistant Cancer Cells with Herceptin (Tz), Kadcyla
(T-DM1) and Se-Herceptin
Click to enlarge.
If the cancer cells act in people as they do in the lab, it potentially means about a fifth of breast cancer patients can get faster, more effective treatment of the disease without requiring as many drugs, which reduces the likelihood of “systemic toxicity,” meaning severe side effects. Less treatment also means a patient's overall hospital bill could be smaller.
“Basically, do you want to drive a Volkswagen or a Ferrari? If you want to drive a fast car, what are you going to drive?” Spallholz asked. “Well, this antibody is kind of like a Ferrari, not a Volkswagen. It works much faster and has a lot more horsepower.”
Breast cancer may not be the only cancer this treatment could affect. The human growth hormone causes uncontrolled tumor growth in a number of different types of cancer.
“Resistance to chemotherapeutic drugs is becoming prevalent and is a major obstacle in the treatment of cancer,” Bapat said.
Is selenium toxic?
Selenium is an essential nutrient for good health; it's in many foods, including Brazil nuts, tuna, poultry and grains. It's also in daily multivitamins, but ingesting too much is potentially deadly. However, the amount included in this cancer treatment would be so small as to not be harmful to humans. It's enough to kill an individual cancer cell when targeted without harming the patient.
Instructor for Minerals in Nutrition, Science of Nutrition, Survey of Biochemistry, and Nutritional Biochemistry. Research area include nutritional and toxicological aspects of selenium and its compounds, drug development using selenium free radical chemistry, arsenic toxicity.
e-mail: Julian Spallholz
The College of Human Sciences at Texas Tech University provides multidisciplinary education, research and service focused on individuals, families and their environments for the purpose of improving and enhancing the human condition.
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The college also offers graduate programs leading to the Master of Science and Doctor of Philosophy degrees.Twitter