Plant-Derived Compounds as Treatments for Cancers: Antioxidants and Chemotherapeutics Introduction The search for more effective medicines for treating cancers continues to be an active area of research. Within the efforts made on this front, the importance of plant-derived compounds needs no introduction. In the past few decades, the improvements in the technology to isolate…
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Plant-Derived Compounds as Treatments for Cancers: Antioxidants and Chemotherapeutics
Introduction
The search for more effective medicines for treating cancers continues to be an active area of research. Within the efforts made on this front, the importance of plant-derived compounds needs no introduction. In the past few decades, the improvements in the technology to isolate compounds from plants have made them an important source of chemotherapeutic agents. At the same time, the antioxidant effects of plant extracts have generated an enormous amount of research around their ability to control the activity of cancers. Given the plethora of available information, it is the goal of this article to review some of the most significant plant-based compounds currently used to treat cancer. We will reference some of the most cited peer-reviewed articles in press, giving any reader a head-start in their research.
Plant Antioxidants – Evidence for Efficacy
During the normal course of cell metabolism, reactive oxygen species (ROS) – compounds containing an oxygen free radical – are produced. These compounds can damage structures within the cell owing to their high reactivity. When cell DNA is damaged, normal mitotic phases can be modified irreparably, which may cause cancer to develop. The human body has several mechanisms to repair damaged cells. Added antioxidant compounds can also deactivate these ROSs before cancerous cells can develop or proliferate.
Polyphenols are a class of compounds containing multiple phenol groups (groups involving a benzene ring with a hydroxyl group). Owing to their resonance structures, polyphenols are powerful absorbers of ROSs. Polyphenols also happen to be produced in significant quantities by plants. One highly-cited review published in the last decade regarding the anticancer effects of phenolics in plants was the one by Dai and Mumper in 2010 (cited over 3000 times, according to Google Scholar).[1] In the section titled “Human Intervention Studies Using Phenolics”, the authors review several experiments done with plant substances in vivo usinghuman subjects for the prevention of cancer. They note that most studies employ tracking of biomarkers of antioxidant or oxidative stress in the human body to serve as determinants on whether a plant improved the body’s ability to control cell damage. These studies seem to show evidence that consuming foods rich in polyphenols reduces the proliferation of cancerous cells in the human body.
In one of the studies Dai and Mumper cited (led by a team at the Ohio State University in the United States), male and female subjects with Barrett’s esophagus – a pre-malignant cancer of the cells of the epithelium of the esophagus – were treated by being given a controlled diet of freeze-dried blackberries. Blackberries are known to contain polyphenols like anthocyanins, which are responsible for their color. The researchers found that consumption of the blackberries significantly reduced the urinary excretion of the biomarkers 8-Iso-PGF2 and 8-OHdG, consistent with the reduction of the oxidative stress associated with Barrett’s esophagus.[2]
Anthocyanins in berries are not the only source of antioxidants from plants which have been found to have anticancer properties. For example, many teas are famous for using leaves which are a rich source of antioxidants. Green tea in particular has been the subject of several studies.
Made from the leaves of the plant Camellia sinensis, green tea is a rich source of a class of polyphenol called catechins – about 30-40% of the dissolved solids in a cup of green tea are catechins.[3] Like anthocyanins, the catechins in green tea feature conjugated double bonds which can neutralize the free electrons of ROSs.[3] In vivo studies have supported the benefits of consuming green tea. A 2003 study by American researchers from the University of Arizona looked at the effects on 40 human subjects who consumed epigallocatechin gallate – a polyphenol abundant in green tea – at doses of 400 mg twice a day for four weeks. They also examined the effect of consuming a mix of all the catechins in green tea at this dose. They found that both regimes, equivalent to 4-16 120 mL cups of green tea a day, were safe and increased body system availability by over 60%. However, they also noted that higher doses exhibited decreasing rates of return on benefits, and even toxicity at much higher levels.[4]
The presence of mixes of antioxidants from different parts of the plants mentioned brings up an interesting point. As noted by at least one literature review, mixes of polyphenols and other compounds from consuming “whole foods” (like the berries and leaves of plants) rather than the isolated compounds individually (like a supplement pill containing just one antioxidant) could have compounding and synergistic effects on their anticancer properties.[5] This is good news, since fruits and tea leaves are often easily obtainable at grocery stores, more enjoyable to consume than supplements, and less easy to over-dose with than pilled compounds.
Plant Compounds used in Chemotherapy
Isolating plant compounds other than antioxidants can bring about powerful treatments in the form of chemotherapy drugs. In some cases, plants are the only economically viable source of drugs for cancer treatment. This is because the compounds are rather complex, making them difficult to create in a factory or lab from the ground-up (a process called total synthesis). Plants, creating these compounds for their own purposes, readily produce them using their biological machinery.
Take the famous example of paclitaxel (Taxol®). Paclitaxel is isolated from Pacific Yew trees (Taxaceae family) at a concentration of around 0.01% by weight (research source cited 188 times).[6] Administered intravenously, paclitaxel’s mechanism of action involves preventing the disintegration of the mitotic spindle fibres of cells during mitosis, causing them to be permanently stuck in the G2/M phase and eventually die.[6] Over the past 3 decades, paclitaxel and its “taxane” derivatives have formed effective drugs against ovarian, breast, and lung cancers.[6] The pacific yew is still the major source of paclitaxel as of 2019. The synthesis of paclitaxel, and increasing the yield of paclitaxel from Taxaceae, is an ongoing research effort.[7]
In another example, the older compounds vinblastine and vincristine, derived from Madagascar periwinkle (Apocynaceae family), are still being investigated for how their derivatives could be used to treat cancers. These “vinca alkaloids” have found use as chemotherapeutic drugs for breast cancers and leukemia.[8] Unlike Taxol, these drugs work by preventing the creation of mitotic spindle fibres, causing dividing cells to be stuck in metaphase and die.
See the highly-cited review by Cragg and Newman (cited over 2000 times according to Google Scholar) for more information on the classical plant-derived chemotherapeutics already in clinical use.[9]
Conclusion
Humankind has been using plants as medicines for thousands of years.[10] However, a deep analytical understanding of their ability to treat cancers has only begun to be made in the last few decades. As research in this article has shown, antioxidants are classified into different types and can be found in a variety of plants. Large-scale studies on all of them and their precise effect on humans will have to be done. Research also indicates that a few very powerful non-antioxidant compounds derived from plants, such as paclitaxel and vinca alkaloids, have saved the lives of thousands of people suffering from cancer via chemotherapeutic means. Research in 2020 is still ongoing to make plant-derived chemotherapeutics more accessible.
References
[1] J. Dai and R. J. Mumper, “Plant phenolics: extraction, analysis and their antioxidant and anticancer properties,” Molecules, vol. 15, no. 10, pp. 7313–7352, 2010.
[2] L. A. Kresty et al., “Transitioning From Preclinical to Clinical Chemopreventive Assessments of Lyophilized Black Raspberries: Interim Results Show Berries Modulate Markers of Oxidative Stress in Barrett’s Esophagus Patients,” Nutr. Cancer, vol. 54, no. 1, pp. 148–156, Jan. 2006.
[3] J. D. Lambert and R. J. Elias, “The antioxidant and pro-oxidant activities of green tea polyphenols: A role in cancer prevention,” Arch. Biochem. Biophys., vol. 501, no. 1, pp. 65–72, 2010.
[4] H.-H. S. Chow et al., “Pharmacokinetics and Safety of Green Tea Polyphenols after Multiple-Dose Administration of Epigallocatechin Gallate and Polyphenon E in Healthy Individuals,” Clin. Cancer Res., vol. 9, no. 9, p. 3312 LP-3319, Aug. 2003.
[5] A. Kapinova et al., “Are plant-based functional foods better choice against cancer than single phytochemicals? A critical review of current breast cancer research,” Biomed. Pharmacother., vol. 96, pp. 1465–1477, 2017.
[6] S. Chandra, “Endophytic fungi: novel sources of anticancer lead molecules,” Appl. Microbiol. Biotechnol., vol. 95, no. 1, pp. 47–59, 2012.
[7] L. Zhu and L. Chen, “Progress in research on paclitaxel and tumor immunotherapy,” Cell. Mol. Biol. Lett., vol. 24, no. 1, p. 40, 2019.
[8] J. Khazir, B. A. Mir, L. Pilcher, and D. L. Riley, “Role of plants in anticancer drug discovery,” Phytochem. Lett., vol. 7, pp. 173–181, 2014.
[9] G. M. Cragg and D. J. Newman, “Plants as a source of anti-cancer agents,” J. Ethnopharmacol., vol. 100, no. 1, pp. 72–79, 2005.
[10] M. R. Montinari, S. Minelli, and R. De Caterina, “The first 3500 years of aspirin history from its roots – A concise summary,” Vascul. Pharmacol., vol. 113, pp. 1–8, 2019.
By Dr.Rao Adeel
Polyphenols are a group of enzymes and chemical compounds that are naturally plant-based, consisting of hundreds of different types, and have been thought to be highly beneficial to your health. If taken regularly, they offer plenty of health benefits, ranging from anti-inflammatory effects, cardiovascular disease prevention, to regulating your metabolic system as well as preventing certain types of cancers to develop. Since polyphenols are naturally occurring phytochemicals, they are exclusively present in green vegetables and fruits. However, certain herbs, spices, dark chocolate, and even wine also contain this compound in abundance. Also, whole grains, nuts, and legumes are also considered to be the source of these phytochemicals. Various health benefits of polyphenols There has been a ton of research on the health benefits of these plant-based phytochemicals, and the results are quite promising and have been linked to its anti-inflammatory, cardiovascular, anticancer and antioxidant properties.
Polyphenols as antioxidants
They have been well-researched on their strong antioxidant properties, which shows that polyphenols, when consumed regularly, can effectively prevent our body from oxidative stress. The question may be raising in your mind that what is oxidative stress? Well,oxidative stress is the resultant action of your immune system against the free radicals
formed in the body as a result of any type of insult, such as infection or an excessive exercise. A good example is the oxidation of LDL ( low density lipoproteins ) or in other words bad cholesterol. After it is oxidised, it sticks to the coronary arteries, causing heart disease. Therefore, it is quite obvious that antioxidant properties of polyphenols not only protect our body from free radicals’ overall damage, but also prevent the heart disease
from occurring.
Anti-cancer properties of polyphenols
Epigallocatechin-3-gallate, or EGCG is an enzyme in the body which is strongly associated in the process of certain types of cancer formation. Polyphenols have the capability of deactivating this enzyme, preventing you effectively against the cancer forming process. Polyphenols have also been strongly associated with their abilities in blocking different kinds of enzyme reactions which cancers essentially need for their growth promotion.
Protective against cardiovascular disease
A research conducted on the relationship between polyphenols and body cholesterols found out that these compounds are not only effective in the reduction of LDL ( low density lipoproteins) or bad cholesterols, but also can significantly increase HDL ( high density lipoproteins) or good cholesterols. Interestingly, HDL’s are considered to be naturally protective against coronary artery disease. In addition, its antioxidant properties
play an important role against chronic inflammation, which is one of the markers of developing heart disease. This is how its two-fold action is incredibly cardioprotective.
Effects on gut microbiome
Polyphenols have a positive phenomenon on your gut health and the mechanism to this is quite intricate . Our intestines are the home to good and bad bacteria which normally maintain a good balance among them. Once this balance is disturbed, for example by consuming unhealthy foods regularly or an excessive use of antibiotics, intestinal problems
start to develop, leading you to have poor gut-health. Surprisingly, vegetables and fruits containing polyphenols, if regularly eaten, have a strong ability in knocking-off bag bugs or bacteria and also help in maintaining a positive balance between the two. It is worth mentioning that this balance is essential for the gut in fighting against the common
intestinal infections such as caused by salmonella, campylobacter jejuni, and Eschericia Coli, which are common bacteria in causing intestinal infections.
Positive Effects on Insulin & Glucose Metabolism: Polyphenols
A rich plant-based diets are capable of increasing insulin sensitivity and lowering your blood sugar levels significantly, shown by research carried out on the polyphenols and their effects on insulin and glucose metabolism. Firstly, these compounds prevent the starch in the food from breaking down into small glucose molecules, preventing the sugar levels from spiking up.
Secondly, it also has a strong stimulus on the pancreas to increase
insulin secretion. Insulin’s main action is to carry blood glucose molecules to the target tissues. This means that polyphenols have a strong influence on the metabolism of blood glucose levels by two mechanisms of action described above. Therefore, regular consumption of polyphenols containing foods can strongly protect you from the risk of developing diabetes mellitus and other chronic health illnesses.
Summary
A plant based diet is rich in polyphenols which play a crucial role in maintaining a good balance between your health and metabolism. From this perspective,as a result, you are naturally protected against a number of serious health conditions which have been discussed above in detail. It is therefore very important for us to develop a habit of eating plant-based foods and a variety of fruits, nuts, seeds, beans and whole grains which are usually rich in polyphenols so that we keep on growing healthier each day.
Oxidative Stress Our skin’s best defense against signs of aging involves protection from oxidative stress. Aside from using a broad-spectrum sunscreen—it is our diet plays an integral role with intrinsic and extrinsic aging. The gradual loss of skin elasticity and sagging is accelerated due to environmental (extrinsic), dietary choices & metabolic processes (intrinsic). Though we…
Collagen- it is the most abundant protein throughout the human body and plays an integral role in maintaining the integrity of the integumentary system. The word is derived from Greek word kolla meaning glue. . (Lodish & Zipursky, 2000) A brief history on the molecular science of collagen:
The physiochemical properties of collagen include two main non-essential amino acids. Molecular structure reveals a polypeptide chain in lengths of 1000 amino acids. (Mayne & Burgeson, 1987) This includes hydroxyl L-proline which is a precursor of proline. The bioactive peptides found in plants help increase the catalytic effect of amino acids needed for the production of collagen. (Tang-Ho, Mussinan, et al, 2013). The biological and pharmacological components in eating a plant based diet provides higher levels of antioxidants that benefit the biosynthesis of collagen in our bodies. In return this means a stronger, healthier body including enhancing our skin’s integrity.
*Some of the food protein sources noted as having antioxidant peptides includes: soy, potatoes, flaxseed, sunflower seeds, bran, quinoa, alfalfa , many other vegetables and fruits (vitamin C).
Advocate for plant based diet and pursuing my PhD in health services- community health advocacy and education. I am a published writer and started journal devoted to this topic and prevention of obesity and other health topics. Thanks for article enjoyed it.
Obesity is an epidemic over 30 % (CDC) of our population is considered obese and the stat is climbing. one which I am focused on with my writing endeavors and in pursuit of my PhD in Health Services- Community health advocacy & education . I appreciate this article- it is insightful, informative and useful. Thanks!