Salinomycin

Salinomycin is an antibiotic that has recently been found to activate cell death in a variety of human cancer cells. It has shown promise in fighting cancer that has a high incidence of drug resistance. What proves to be quite promising about salinomycin is that it has been found to destroy cancer cells of different origins while not harming normal cells. It also appears to be effective against a variety of cancers including breast, prostate, ovarian, as well as several others. The following information provides a brief history of salinomycin, how it is made, its current use, and possible future use.

Researchers in Japan isolated salinomycin in the early seventies. It was registered in 1978. It had been discovered that salinomycin demonstrated antimicrobial activity. The salinomycin was produced through tank fermentation and then the culture broth was filtrated. It was then purified, dried, and eventually crystallized. Through X-ray analysis the research discovered that salinomycin was related to the monocarboxylic polyether family of antibiotics. Salinomycin was then tested on chickens with coccidiosis, which is an intestinal disease affecting both humans and animals. The antibacterial drug was effective and has been used since in a variety of livestock as an anticoccidial drug. Studies done in 2009 and 2011 showed that the use of salinomycin could induce cell death of human cancer cells. It has been shown to kill breast cancer stem cells in mice.

Promise

Salinomycin is promising primarily because it has been shown to kill the cancer stem cells while at the same time enabling other drugs to more efficiently kill the regular cancer cells. This dual effect of killing both cancer and cancer stem cells is necessary to completely eradicate the cancer and prevent relapses. Since salinomycin can be dangerous, even fatal in humans, much more research and testing needs to be completed before this drug is a regular part of cancer therapy in humans. The potential at this time is very encouraging, however. It’s possible that salinomycin could be the miracle drug of the future in the fight against cancer. It could be coupled with the current drug therapies that fight specific types of cancer, with one drug targeting the regular cancer cells and salinomycin targeting the stem cells. If the specific dosage and ways to administer the drug can be found at safe yet effective levels, the potential benefits of salinomycin could prove to be a huge breakthrough in the war on cancer.

Salinomycin is a polyether made by a strain of streptomyces albus. Streptomyces is a form of bacteria, usually found in soil but sometimes on plants and animals, and is a source for several antibiotics. Salinomycin has shown to be an antimicrobial agent when used against gram positive bacteria and even certain types of fungi. It has not been shown to work against gram negative bacteria or yeast. It has also been effective in destroying a variety of parasites.

One of the interesting aspects of possibly using salinomycin for cancer treatment is that it’s an antibiotic while most cancer drugs currently being use are chemotherapeutic agents. Antibiotics are naturally occurring substances that originate from microorganisms. Chemotherapeutic drugs are synthesized chemically.

Salinomycin is usually a white, yellowish powder with a slight odor. It is soluble in a variety of substances, but almost never soluble in water. After salinomycin is produced the components of the drug stay stable and it is easily mixed into feed for animals.

The drug is generally defined as a polyether potassium antibiotic which can change cellular function and metabolism. It affects sodium and potassium at the cellular level and is chemically classified as an Ionophore. It is solid in its physical state and should be stored at -20 C. It is recommended not to freeze salinomycin in this form.

There have been some concerns regarding the production costs for salinomycin. Costly organic solvents are used in the production of this compound. Proper disposal of waste is required when manufacturing salinomycin. The entire process can be quite expensive.

Uses of Salinomycin

Salinomycin is currently approved by the FDA in the United States and is used around the world. It is used as a supplement in poultry feed, and in particular for broiler chickens. It is a bestselling feed additive for chickens and contributes to producing millions of tons of disease free chicken meat throughout the world.

Salinomycin is currently used primarily to control coccidiosis in the broiler chickens. Coccidiosis is an intestinal disease that can spread from one animal to another, especially those living in close contact. Chickens become droopy in appearance and begin to huddle together. They often look dirty and don’t eat or drink much. After a few days there is noticeable blood in their droppings. Salinomycin acts against three different stages of this parasite’s lifecycle.

Not only has the use of salinomycin been used to control coccidiosis, but the use of this drug has led to a decrease in necrotic enteritis in chickens. Necrotic enteritis is caused by clostridium perfringens and is a disease in poultry that causes immobility, dark diarrhea, changes in feathers and eyes, and sometimes sudden death in otherwise healthy chickens. This disease can spread quickly through flocks and cause significant damage. Humans can get food poisoning from the diseased meat that is not cooked to a high enough temperature.

It has been reported that using salinomycin may also reduce salmonella in chickens. Finally, salinomycin is also used in a variety of animals to improve nutrient absorption.

In spite of the many benefits of using salinomycin to prevent various ailments in chickens there is the risk of overdose. The drug produces severe toxicity when it is accidentally ingested by animals in higher than recommended doses. This happened in the Netherlands in 1996 when cat food was contaminated with salinomycin. Some of the cats experienced partial paralysis, especially in the hind limbs. In some cases there was even respiratory failure and death.

Salinomycin poisoning in turkeys has been reported on several occasions. In one particular incident a flock of turkey hens were accidentally fed a mix containing salinomycin sodium. The result was that almost 35 percent of the flock died. Even though the antibiotic is used for broiler chickens, it is not recommended for laying chickens or chickens that are breeding.

Promises

Salinomycin seems to have the most promise in the fight against colon and breast cancer. It may possibly help destroy other cancers, including those in the head and neck.

Studies done on mice have shown that salinomycin may directly target cancer stem cells. There is increasing evidence that cancer stem cells play a critical role in the recurrence of cancer. The stem cells are a subpopulation within the tumor cells that have the ability to regrow. Cancer deaths are still relatively high because current treatments fail to destroy the cancer stem cells. When the stem cells survive, the cancer is more likely to recur, even if the tumor has been shrunk by conventional cancer treatments. Relapse is more likely when stem cells are allowed to survive.

Oncologists currently have many therapies to attack cancer; yet often the tumor regrows even after treatment. Research has shown that it is difficult to isolate and destroy the cells inside of tumors that contribute to regrowth. These cancer stem cells have proven difficult to grow outside of the body so they can be studied more closely. A study group eventually found a way to manipulate breast cancer cells and turn them into cancer stem cells so different chemical compounds could be tested on them.

Approximately 16,000 varieties of chemical compounds were then used on these cells. After testing, the researchers narrowed the compounds down to 32. Finally, it was narrowed down to one compound: salinomycin. Salinomycin was better at destroying the breast cancer stem cells than the most often used chemotherapy agents.

Salinomycin was even found to be effective against genes associated with extremely aggressive tumors. Salinomycin was recently found to be effective in treating various lung cancers, ovarian cancer cells, and cancers of the prostate.

Prostate cancers often will initially respond to standard therapies. However, when relapse does occur, the new cancer cells are often then resistant to the usual treatment. Studies have shown that salinomycin is able to inhibit prostate cancer cells without harming the non malignant prostate cells.

Not only does salinomycin combat the cancer stem cells but recent studies have shown that salinomycin was capable of making general cancer cells more susceptible to other cancer fighting drugs such as Paclitaxel. Because salinomycin shows potential for destroying the very roots of cancer growth, namely the stem cells, it may be used to treat a variety of advanced cancers. What is interesting about this is that the salinomycin causes different reactions when fighting cancer stem cells.

Researchers have been trying to discover exactly how salinomycin targets and kills cancer stem cells. Some studies seem to indicate that the drug acts as an inhibitor of what is biologically known as ABC transporters. ABC transporters are necessary for the viability or survival of a cell. In other words, salinomycin works in this way to help destroy the cancer cells. The drug not only inhibits these cancer stem cells but helps overcome drug resistance that happens in some patients. Salinomycin may also inhibit the signals and pathways in cells that are necessary for stem cell development.

Salinomycin may also be used to treat African Trypanosomiasis which is a parasitic disease commonly referred to as sleeping sickness. There are a few treatment options for this disease, but they are considered outdated. There is also the problem of resistance and toxicity. Salinomycin may be effective in treating Trypanosomiasis because it can cause an influx of sodium, thus causing the cells to swell. Salinomycin creates potassium imbalance in cells. When treating this disease the salinomycin can be given as an oral medication. Current treatments are usually injected.

The costs of producing salinomycin for its current use is expensive. This could prohibit future studies and use in humans. At the current time, however, producing salinomycin sodium is much cheaper than regular salinomycin. Some research has suggested there is little difference between salinomycin sodium and salinomycin in fighting cancer stem cells.

Dangers

Because of the severe toxicity of salinomycin in several animals, the drug was never tested and validated for human use. Scientists suspect It has the potential to cause severe heart and muscle problems. Prescribing the correct amount of salinomycin and establishing safe dosing schedules for humans are not possible without further data. A major concern is how quickly the toxicity and overdose may occur. Salinomycin is rapidly absorbed and metabolized in animals. It is quickly eliminated from the body and there is little residue of the compound in cattle a few days after ingestion. Scientists would have to figure out this quick absorption and elimination would affect humans.

The manner in which salinomycin destroys bacteria is different from how it destroys cancer stem cells. It is still too risky for human use. Extensive research must be completed on the drug and its possible side effects before clinical trials in humans could be attempted.