New discovery of horse snake venom protein that can kill cancer cells and protect brain nerves

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(Kuala Lumpur News) Ikeshan, a PhD in Molecular Neurobiology from the Faculty of Medicine and Health Sciences, Monash University, Malaysia, led his school to conduct various experiments using snake venom proteins, including studying which snake venom proteins can kill cancer cells and protect the neurons of the brain.

Has at least 15 enzymes

Professor Iekhsan Othman, Ph.D. in molecular neurobiology, pointed out that the main purpose of snakes to produce venom is self-defense, and the second is to use venom to paralyze their prey to capture them smoothly, and it is definitely not used to attack or kill humans.

“There are at least 15 kinds of enzymes in snake venom, most of which have the function of degrading red blood cells, muscles, nucleic acids and proteins of various organisms, so once snake venom enters the body of the prey, it will quickly begin to decompose the cells and tissues of the prey. will help the snake devour its prey.”

He said that snake venom is a complex mixture. In addition to enzymes, there are many different biologically active proteins in snake venom that can specifically target different organs and tissues in organisms. They can be classified into muscle toxins (myotoxins) in terms of their toxic effects. , neurotoxins (neurotoxins), cardiac toxins (cardiotoxins) and so on.

“for example,

Neurotoxins can target the epineurinous membranes of neurons in humans

(presynaptic membrane) and combined with it,

so that the latter cannot produce neurotransmitters (neuro transmitter),

This blocks nerve conduction and inhibits the nerve from functioning normally. “

“Among them, the phrenic nerve located on the human diaphragm is the most exposed neuron in the human body. Once the snake venom invades the human body, it will first target it and paralyze it, so that the poisoned person cannot effectively use the expansion of the diaphragm. and contraction for gas exchange, and eventually die of asphyxiation.”

In general, we all think that any substance in snake venom is harmful, but in the long course of medical research, we found that some proteins in it have their own benefits.

He mentioned that the application of snake venom in medicine is not new. For example, some proteins that can relax blood vessels have been isolated from the venom of the Brazilian spearhead viper (Bothrops jararaca), called bradykinin potentiating peptide, and it has also been successfully developed into two clinical The blood pressure-lowering drugs used are called captopril and enalpri, both of which are angiotensin converting enzyme inhibitors (ACEI).

separated by instrument

“In our country, as early as the 1970s and 1980s, surgeons began to use anticoagulant snake venom protein (named arvin) to perform operations. Surgeons will inject arvin for patients before the operation to prevent the patient from cutting the patient’s skin. Blood clotting in surgical wounds can cause various thrombotic complications. Arvin is actually taken from the Malayan pit viper, which was developed by the National Institute of Medical Research (IMR) at that time.”

As a neurobiologist, Professor Iksan is interested in using snake venom as a tool to study neural function in the brain. Basically, he looked for specific proteins in snake venom that have an effect on exocytosis.

Exocytosis refers to the process in which synaptic vesicles in nerve cells release neurotransmitters into the synaptic cleft, so that nerve messages are transmitted to the next nerve cell.

“When I was still studying for a Ph.D. at Imperial College London, they were already using many components in various snake venoms to study human neurological functions. Basically, we will separate various components in snake venoms through sophisticated medical instruments. , and then see which snake venom components will target and bind to the presynaptic membrane of which neurons.”

most studied snake species

“At that time, I was studying the Taiwanese krait in the UK. After I got my doctorate, I returned to Malaysia and started to study the local snake species. You know, Malaysia is one of the seven countries with the richest biodiversity in the world. One, here we have a variety of snakes, such as the Malayan krait and the banded krait, which are the most venomous snakes.”

He mentioned that, in fact, none of the local venomous snakes is fully understood, including the cobra and krait. Pit viper (viper) is the snake species with the most research, because it often appeared in rubber plantations in the 1970s and 1980s. It looks like dead leaves of trees, and rubber tapping workers often step on them accidentally and get bitten.

From discovery to exciting results

Professor Ikeshan is also actively looking for which snake venom protein can directly kill cancer cells through the principle of cytotoxicity. The ideal is to find a snake venom protein that only kills cancer cells and does not kill other normal cells. Many of the side effects of today’s cancer chemotherapy, such as reduced immunity, can be avoided.

“Basically, we will experiment with various cancer cell lines that we have in our institute. There have been two new discoveries. First, we have found that the Malaysian red-mouthed viper (Calloselasma rhodostoma) and the mangrove forest The snake venom protein of Cryptelytrops purpureomaculatus can successfully kill 70% to 80% of colorectal cancer cells, but it also kills other normal cells.”

in laboratory testing

“Furthermore, we also found that snake venom proteins from Bungarus candidus and Bungarus fasciatus have anticancer activity against neuroblastoma and glioblastoma cancer cells. “

“But these studies are at the stage of laboratory experiments, and these experiments are carried out using the whole snake venom (that is, all the components and proteins in it), and we have not yet been able to clearly point out which protein in the snake venom has potential anti-inflammatory properties. Cancer activity, so our next research work is to separate and purify each component of these snake venoms precisely.”

Fortunately, there is a precision instrument called LC-MS (Liquid Chromatography–Mass Spectrometry) in the laboratory of the Faculty of Medicine and Health Sciences where he teaches, which can help us separate the components in snake venom and tell us What kind of snake venom protein (venom protein, venomic) is there.

Cobra Contains Neuroprotective Protein

“In our institution today, we use rhodopsins for a variety of experiments, including looking at which snake venoms kill cancer cells and which snake venoms protect neurons in the brain.”

He said that it has been found that a protein in the venom of the Sumatran cobra (Naja sumatrana) has a strong neuroprotective effect and can protect neurons from degeneration. Although this is still in the research stage, the results discovered now have Very exciting. Because whenever we talk about dementia, Alzheimer’s, Parkinson’s, epilepsy, it’s the abnormal functioning, degeneration, and death of neurons.

Do not raise or make snake medicine without authorization

Question 1. Is there any anti-cancer drug made from snake venom that has been approved for clinical use in my country?

Answer 1. As far as we know, not yet. Although there are a large number of different related studies abroad, most of them are in the research stage, and American snake species and Brazilian snake species are often used for research.

We must be clear that the problem with cancer is that cancer cells have multiple mutation factors, and the behavioral characteristics of each cancer cell are also different. What’s more, no one has yet identified the mechanisms that induce the uncontrolled proliferating of various cancer cells. Just like our experiments found that the above-mentioned snake venom protein can only kill 70% to 80% of colorectal cancer cells, even if it kills the remaining 1%, the cancer cells will grow and mutate again.

Q2. Where did you collect snake venom?

Answer 2.There is a snake garden on the Batu Pahat River in Perlis, which used to be used by IMR to develop antivenom (antivenom), but later, the cost of quality control was too high, and the death rate due to poisonous snake bites in our country has increased. If the rate is reduced (only 2 cases in 2018), IMR will not manufacture antivenom in the snake farm, but instead purchase antivenom from Bangkok, India, Indonesia or Taiwan.

Today, the snake farm has become a tourist attraction, and it has also become a place for us to collect snake venom.

Question V3. How to store snake venom?

Answer 3. We will freeze the liquid snake venom first, and then put it into a special device to transform it into a powder form. Only in the powder state can the snake venom preserve its active ingredients for a long time.

Question 4. Although the protein in snake venom has medicinal uses, ordinary people should not raise snakes at home or use the venom produced by snakes as medicine, right?

Answer 4. Yes, that is very dangerous, people must not do this.

The snake venom research we conducted was carried out under very safe and cautious procedures and measures. If you are not careful, there will be a risk of poisoning. For example, if you accidentally let the powdered snake venom touch any part of the skin, it will also cause poisoned.

In addition, the public should not raise snakes at home by themselves, because the public has very little knowledge of snakes, and it is impossible to distinguish between poisonous snakes and non-poisonous snakes. Just like a family in Sabah who did not know that puffer fish contained a large amount of tetrodotoxin and ate it by mistake, resulting in the death of the whole family.

Text Zeng Yongtai

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