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Influence of Plant Secondary Compounds on Cancer

What are plant secondary compounds?

Secondary compounds also known as secondary metabolites are defined as organic molecules that serve a particular function in the plant.

They are called secondary simply because the growth and development of the plant are not dependent on these substances. On the other hand, primary metabolites are vital for a plant’s sustainability and growth (e.g. amino acids, lipids, nucleotides).

There are approximately 200,000 compounds that result from secondary metabolism, each compound has a role. Most of these secondary compounds are synthesized to protect the plant against its environment and neighbor plants, produce pigments to give the plant a particular color, and attract beneficial organisms such as pollinators.

Humans have used these substances for millennia as medicines, dietary supplements, and spices for cooking.

Before the introduction of industrial-scale synthesis of pharmaceutical drugs, people used to treat medical conditions using these plants; what they didn’t know back then is that they’re using these secondary metabolites as drugs. For example, substances like cocaine, caffeine, nicotine, and atropine are all secondary metabolites used by humans in the past and are now produced in massive scale for medicinal purposes.

History of cancer

Cancer has been around for as long as humans have been around. It’s one of the rare diseases that has been discovered for centuries; yet, we still don’t have a cure.

The first case description was as far back as 1600 BC in ancient Egypt. By the 17th century, physicians started dissecting the bodies of patients to figure out the cause of death and the presence of cancer was established but no definitive cause was attributed to any type.

What exactly is cancer?

The pathophysiology of cancer is very complicated. but let’s keep it simple.

Usually, the cells in our bodies have a certain duration to live called the lifespan, after which the cell will die; a process referred to by the fancy term “apoptosis”.

This applies to every cell in our bodies except muscular and nerve cells, for example, red blood cells have a lifespan of 120 days whereas the cells in our small intestines live for about 1-2 days.

After the death of the cells, new cells are generated to replace them. This is a physiological process that takes place every minute in the organism.

This process is controlled by the genetic codes located in our DNA.

Now that you are familiar with normal cell cycle physiology, let’s talk about cancer.

When a genetic mutation happens, this process is disrupted. Normal cellular cycle goes haywire and cells start to grow in an uncontrolled anarchic manner; cancerous cells start to grow in number at an incredible pace destroying everything in its way and consuming a huge amount of nutrients and oxygen.

This is cancer in a nutshell.

Without even realizing it yourself, you might have concluded a very important thing: cancer happens to cells that are always dying and being generated.

That’s a major concept in oncology (the science of studying cancer). You’ve probably never heard of cardiac cancer, right? This is because cardiac cells are muscular cells, and as I mentioned earlier, muscular cells don’t have a limited lifespan. Instead, they live for as long as the host (You and I) lives.

I could almost hear some of you saying “but you also said nerve cells don’t have a lifespan, why do we always hear of brain cancer?”

That’s an excellent question, the answer is simple. Brain cancer is not originated from nerve cells but from the cells responsible for the protection and nutrition of nerves such as glial cells and astrocytes.

Congratulations! You’ve become expert oncologists.

The relationship between secondary metabolites and cancer

 

Polyphenols can help with cancer

 

As science and medicine progressed, doctors and researchers became more familiar with cancer, how it develops, how it spreads, and what causes it.

This has led to the introduction of many chemical substances in an attempt to treat cancer; nowadays, it’s called chemotherapy.

Many drugs used in chemotherapy today are derived from plant secondary compounds. For example, vincristine, vinblastine, and vinorelbine are all alkaloids which are a class in the secondary metabolites family. Other chemotherapy agents that are secondary compounds include etoposide, teniposide, docetaxel, irinotecan, etc.

To top it all off, many plant secondary compounds are currently in preclinical and clinical trials.

It is important to note that some compounds have been found to possess anticancer properties, but couldn’t be used clinically due to their poor bioavailability and/or toxic side effects.

It’s not all bad news though, plant secondary metabolites are oftentimes thought of as gateways to develop new drugs; by modifying the chemistry of these compounds we can keep the anticancer properties and at the same time increase the bioavailability or decrease the toxicity of the drug. It’s not as simple as it sounds, believe me!

Now that we’ve established that these substances can be used as chemotherapeutic agents to treat cancer, let’s briefly discuss some of the secondary metabolites that are in clinical trial to be used in the future as anticancer agents.

Ingenol Mebutate

When phytochemistry experts started studying Euphorbia peplus, several molecules were discovered including Ingenol mebutate. This substance turned out to have the most active antitumor components in the plant.

It was found later that Ingenol Mebutate is most effective against non-melanoma skin cancer.

The results of multiple studies and experiments conducted have been encouraging towards using Ingenol Mebutate as a skin cancer drug but further investigation needs to be done. Currently, it’s still in clinical trial.

Curcumin

Curcumin is a polyphenolic compound that has been extracted from the rhizome of turmeric (Curcuma longa L.), a tropical Southeast Asia plant mainly used as a spice.

It has been used for millennia to treat many maladies due to its anti-inflammatory and anti-oxidant properties.

Research around the anticancer properties of curcumin has been launched based on the low occurrence of mucosal gastrointestinal cancer in Southeast Asia and the almost-daily use of turmeric in their diet.

Curcumin has proven to be effective against solid tumors in vitro (in the laboratory) and also in some in vivo (on lab rats and/or humans) cases.

Cancers such as brain tumors, pancreatic, lung, breast, leukemia, prostate, skin cancers, and hepatocellular carcinoma have all shown to be sensitive to curcumin therapy in the experiments conducted.

Moreover, curcumin has shown to possess a chemosensitizer effect on some anticancer agents (e.g. gemcitabine, paclitaxel and 5-fluorouracil, doxorubicin). In other words, it increases the sensitivity of cancer cells to the chemotherapeutic agents.

Time for the bad news, curcumin has extremely low bioavailability due to its poor absorption, thus mandating patients to consume 8-10 grams of free curcumin orally every day in order to reach the therapeutic dose and becomes effective.

Researchers are trying to find a way around this problem by using techniques such as adjuvant therapy and nanotechnology.

There are 17 open clinical studies of curcumin uses in cancer therapy today; hopefully, we’ll hear some good news soon enough.

Betulinic Acid

Betulinic acid was first identified and isolated from Gratiola officinalis L. and named “graciolon”.

Its anticancer properties were first discovered in 1995 by a researcher at the University of Illinois; rats with melanoma injected with this substance were cured. Since then, many researchers have been testing the effects of betulinic acid against melanoma and more recently, against many types of cancer.

Conclusion

As cancer takes more lives every year without real signs of a definitive cure, and as the drugs available in the market nowadays have issues such as serious side effects and resistance from tumor cells; it becomes essential to find alternative drugs with anticancer properties.

This is where plant secondary metabolites come in; these substances are naturally-derived, thus the potential side effects might be less harmful such as the case of curcumin.

Fortunately, researchers are working day and night to find new substances as well as conduct clinical trials for already-established molecules with chemotherapeutic properties.

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