Scorpion Venom: An Unexpected Weapon Against Cancer
Biology

Cancer is a disease which occurs when changes in a group of normal cells within the body lead to uncontrolled cellular growth. This causes a lump which is called a tumour. If left untreated, tumours will grow and spread (metastasis) into the surrounding normal tissue, or to other parts of the body via the bloodstream and lymphatic systems. Metastasis negatively affects the digestive, nervous and circulatory systems of the body.
There is no single cause for any one type of cancer, which is why cancer is a difficult disease to eradicate. Some causes and catalysts for cancer are unavoidable, however, some can be avoided and/or abstained from.
Cancer-causing substances (carcinogens) found in the environment can cause cells to mutate and become cancerous. Different mutations or changes to the genes can alter how a healthy cell behaves. For example, a mutation could mean that too much or too little protein is made inside the cells. However, more than a few genetic mutations need to have occurred in order for a cell to be cancerous. An example of a carcinogen is tobacco. Tobacco smoke contains at least 80 different carcinogenic agents. When smoke is inhaled, the chemicals enter the lungs, pass into the bloodstream and are transported throughout the body. The more a person smokes, the younger they start, and the longer they keep smoking, increases the risk of cancer.
Another example of a carcinogenic is radiation. The main risk with radiation is having prolonged and unprotected exposure to ultraviolet rays. These are some of the avoidable causes of cancer.
As mentioned earlier, there are some unavoidable causes. One example is genetics. Some people are born with a genetically inherited risk for cancer (this is called genetic predisposition). This doesn’t guarantee cancer, but it definitely increases their chances to be diagnosed. For example, women that have the BRCA1 and BRCA2 breast cancer genes have a higher genetic predisposition to developing cancer. Another example of an unavoidable cause for cancer is age. Many types of cancer become more likely as a person gets older. This is because the longer a person lives, the more exposure they have to carcinogens.
Since cancers grow in tumours, it is important to understand what the different types of tumours are. There are two types of tumours: Benign tumours and Malignant tumours. Benign tumours are cancerous but do not threaten life. They tend to grow quite slowly. They also do not spread to other parts of the body and are usually made up of normal and healthy cells. They only cause problems when they grow very large as they cause discomfort when they begin to press on organs. Malignant tumours grow faster than benign tumours. They have the ability to spread and when doing so, they destroy healthy cells. Malignant tumours can break often break off from the primary tumour and spread to other parts of the body through metastasis. The tumours invade healthy tissue and they continue to divide and grow.
It is clear that malignant tumours/cancer cells are different than healthy cells. Cancer cells are not specialized like healthy cells. For example, cancer cells do not multiply/divide for any particular health related issue like normal cells. The reason they multiply/divide with no particular reason is because cancerous cells are able to ignore signals that tell them to stop dividing or start the process of apoptosis (a process that gets rid of unneeded cells). Another example is that cancer cells are able to induce healthy cells to create nutrients for them. They induce normal cells to produce blood vessels which supply tumors with oxygen and nutrients.
The genetic changes that contribute to cancer tend to affect three main types of genes: proto-oncogenes, tumor suppressor genes, and DNA repair genes. Proto-oncogenes are involved in normal cellular growth and division. When these genes are altered, they may become cancer-causing genes allowing cells to grow and survive when they should not. Tumor suppressor genes are also involved in controlling cell growth and cell division. Cells with alterations in tumor suppressor genes may divide in an uncontrolled manner. DNA repair genes are involved in fixing damaged DNA. Cells with mutations in these genes develop additional mutations in other genes. Together, these mutations may cause the cells to become cancerous.
Cancer as of date is still persisting and becoming even more deadly. However, scientists are trying to find a cure and manage different types of cancers.
The main treatments for cancer are chemotherapy and surgery to get rid of malignant tumors. Chemotherapy causes extreme side effects like fatigue, pain, permanent damage to organs. Surgery is unpredictable and many times leaves a part of the tumour behind, which allows it to metastasis again. With the help of recent studies and research, scientists have more dependable and safer ways to cure and manage cancer. An unexpected cure has been found to exist in Scorpion Venom.
Before scientists used scorpion venom, they first studied the composition of the venom. Scorpion venoms are very complex mixtures with hundreds of different components. The venom is made up of mucosa, oligopeptides, nucleotides, amino acids, ions, neurotransmitters, salts, water and low molecular weight peptides. It also include enzymes such as phospholipase, hyaluronidase, lipase, alkaline phosphatases, and proteolytic enzymes.
Scorpion venom peptides are generally classified into two main groups: Disulfide bridged peptides (DBPs) and Non-disulfide-bridged peptides (NDBPs). Disulfide bridged peptides (DBPs) usually target membrane bound ion channels. The membrane bound ion channels targeted by the DBPs family of scorpion peptides are the Na+ (sodium), K+(potassium), Ca2+ (Calcium) and Cl−channels (Chloride). These channels help regulate normal cellular physiology. By disrupting the function of these channels by interacting with scorpion venom peptides can result in significant alterations in their normal function, leading to the several symptoms developed in mammals during scorpion envenomation. This disruption, where cancer is involved, allows for the venom to break apart the cancer cells, which kills them. Non-disulfide-bridged peptides (NDBPs) have several biological functions such as anticancer, anti-inflammatory, antimicrobial, hemolytic, bradykinin potentiating and immune-modulatory activities.
Scorpion venom used in different ways for various cancers. The venom is used to light up glioma cells. Glioma is a form of brain cancer that is resistant to medical and surgical treatment. The scorpion toxins are used to treat cancer patients by injecting fluorescent molecule bonded with a scorpion toxin peptide called chlorotoxin into cancerous tissue to show tumor boundaries. Glioma cells have expressed a glioma-specific chloride ion channel (GCC) that is sensitive to chlorotoxin (CTX) that is found in cancer cells. Chlorotoxin (found in Death Stalker scorpions) helps to with early detection of glioma cancer cells and could save many lives. BmK AGAP is sodium channel-specific neurotoxins found in scorpion venom which shows potential to kill cancer cells. BmK AGAP toxin has been to inhibit the growth of glioma by inducing apoptosis.
Scorpion venom helps fight Leukemia too. Leukemia is a cancer of the bone marrow or blood caused by an abnormal rise of immature white blood cells. From the Indian scorpion, a protein called bengaline is isolated. Bengalin possesses apoptogenic, cytotoxic and antiproliferative activity against chronic myelogenous leukemia and histiocytic lymphoma. Bengalin provides a molecular mechanism for the anticancer effect on human leukemic cells resulting by mitochondrial death of cancer cells.
Jim Olson is a pediatric oncologist whose research is all about scorpion venom to light up cancer cells. He is running this project at the Fred Hutchinson Cancer Research Center in Seattle, Washington. He leads a team who has succeeded at creating a “tumour paint.” This tumour paint attaches to cancer cells and lights them up so it is easier for surgeons to operate successfully and leave no trace of the cancerous cells. Dr. Olson retells a story of a patient who had brain tumour surgery but it left much of her tumour behind. This is because the surgeon thought the tumour was part of the normal brain. This is a common problem that occurs in tumour surgeries. So, Olson and his team became committed to developing technology that would light up cancer cells. Olson and his team focused on the scorpion toxin chlorotoxin found in Death Stalker scorpions. Since Death Stalker scorpions paralyse their prey, it became evident that the target Chlorotoxin affects the brain. Adding on to that, Chlorotoxin target seemed to be found in cancerous brain cells not normal brain cells. To test their theory, they grew a human tumour on the back of a mouse. Olson and his team connected the toxin to a fluorescent tag (called the molecule BLZ-100) and injected it into the mouse. Soon enough, the cancer was brightly glowing. In 2015, the FDA approved the first clinical trials of BLZ-100. The results so far have shown that BLZ-100 is in fact lighting of the cancer cells and have shown that patients are not negatively affected by the BLZ-100 molecule. However, trials are still being conducted. Since the study of the usage of scorpion venom is still in its early stages, the practice is not widespread but soon the BLZ-100 molecule will revolutionize how humans deal with cancer.
Laura Leticia Valdez Velazquez is a professor and researcher at the University of Colima in Mexico. She is in charge of a laboratory called "Laboratory of biological products" in which her team and she are dedicated to the characterization of poisons of scorpions. Through her work she has found that sodium and potassium toxins in scorpion venom are toxic to cancer cells. The toxins affect the ion channels in the cell membranes of cancer cells. These toxins can block these channels causing an imbalance in the cell and leading to its cellular death. Dr. Velazquez and her team have also found proteins in the venom that damage the membranes of the cells. Velazquez isolates the sodium and potassium toxin from the full compound of the venom of the Alacran centruroides tecomanus scorpion. Only preclinical studies have been done for the use of scorpion venom to kill cancer cells. However, the venom of Centruroides tecomanus has been tested on cells with cervical cancer and lymphoma cells. And through comprehensive analysis of Centruroides tecomanus reveals compounds with antimicrobial and cytotoxic activities. When this study goes into clinical trials it has strong potential to cause a cancer cure.
Work form Jim Olson and Laura Leticia Valdez Velazquez shows the great advances that scientists are making towards the cure of this dreaded disease. The work of these prominent Scientists, along with many others in world, has given hope that cancer may be a beatable disease. It may take decades to get to a point where Dr. Olson’s and Dr. Velazquez’s research is used world wide. However, these significant advances in science will provide more information on cancer research and will inevitably, bring about a cure for different cancers that plague our society today.




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