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Plant Compounds & Cancer

Author:
Sheilah Fulton
Categories:
Anti-inflammatory

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.