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Juglone: A New Cancer Treatment

Research paper by: Marisa M.


New Potential Cancer Treatments

The American Cancer Society estimates that there will be 1.8 million new cases of cancer and 606,520 cancer deaths in 2020 in the United States (2020). Almost 17 million people in the United States as of right now have had or still have some type of cancer. Many people have now been looking into prevention options for development of cancer (American Cancer Society, 2020).


Discussion

Cancer Treatments

There is no specific cure for cancer, however there are treatments that can potentially cure certain cancer patients. Cancer is most commonly treated with either surgery, chemotherapy, or radiation. However, with these types of treatment one can experience nausea, pain, diarrhea, and fatigue (American Cancer Society, 2020).

There are complementary therapies available to use alongside these conventional medical treatments, including a well balanced diet. The body needs a constant source of protein, carbohydrates and fats to fight against the cancer and stay healthy (Cancer Research UK, 2020). Besides following a diet during one’s cancer treatment, there have been certain foods shown to prevent cancers from developing. All nuts have been used to support a healthy-based diet, even though each type of nut has various nutritional densities. Walnuts, in particular, have been extensively researched regarding cancer preventive diets. Walnuts have been proven to “decrease oxidative stress, inflammation and gene expression that can lead to cancer” (American Institute of Cancer Research, 2020).


A black walnut tree. Photo from: The Spruce


Juglandaceae

The whole walnut family is called the Juglandaceae. Besides being known for their edible walnuts, these trees are also known for their valuable wood. (Sibley, 2009). One of the most popular species of walnuts are called Juglans nigra, or more commonly known as the black walnut tree (Habtemariam, 2019).


Allelopathy is a particular form of organismal interaction that only occurs in plants (Pidwirny, 2006). In the process of allelopathy, “...plants provide themselves with a competitive advantage by putting phytotoxins into the near environment…” (Wu, Pratley, Lemerle, Haig & An, 2001). These phytotoxins are chemicals that kill plants susceptible to its poison (Inderjit & Duke, 2003, p. 531). One such plant is Juglans nigra, which is known to kill many crops (Thompson, 1985). The chemicals that allelopathic plants release can be called allelochemicals. “Allelochemicals are metabolic by-products of certain plants that, when introduced into the environment, cause growth inhibition,” which affects cell reproduction, respiration, and food intake (Harris et al., 2015, p. 2).


Juglone is the name of the chemical that the black walnut tree releases to provide itself a competitive advantage (Sibley, 2009). Juglone is formed when hydrojuglone glucoside is released, and exposed to air and soil compounds, after being washed down by rain through a process called leaf latching (Moore, 1982).

Photo from: RsearchGate


Hydrojuglone glucoside can be found in the leaves, stems, fruit hulls, inner bark, and roots of the black walnut tree (Harris et al., 2015). Even though the black walnut tree can emit its toxins up to 80 feet away from its trunk (“Black Walnut Toxicity”, 2019), not all plants are affected because as Terzi (2008) explained, “Some plants appear to have a protective capacity against oxidative stress from juglone by emitting enzymes that metabolize the compound to less toxic hydrojuglones…” (p. 1,871). The less fortunate experience leaf wilting, yellowing, and eventually death (Mccoy, Utturkar, Crook, Thimmapuram, & Widhalm, 2018).


Hans Molisch

The term “allelopathy” was created by Austrian plant physiologist Hans Molisch in 1937, and comes from the German “allelopathie,” meaning to inhibit interactions of plants through chemicals (Willis, 2007). Molisch states that there are good and bad outcomes related to allelopathy, but that people usually just see the harmful effects (Willis, 2007).

Ethylene

Molisch’s experiments revealed that fruits’ growth was reduced when a certain compound ethylene was decreased by allelopathic chemicals (Rice, 1974, p. 220). Ethylene is a gas found in plants’ hormones, promoting growth in fruits (Carey, 2019). Allelochemicals inhibited the fruits’ abilities to grow and decreased the production of ethylene (Rice, 1974, p. 323), causing the plant to die. The allelochemicals were able to target the component in fruit that caused their growth.

Mammary adenocarcinoma

Similar to allelochemicals targeting ethylene in fruit, the allelopathic black walnut tree is known to target certain growth components as well. As stated by Aithal (2012), the juglone produced by the black walnut tree can suppress the growth of mammary adenocarcinoma, or melanoma tumors, in Swiss albino mice (p. 69). Juglone not only impacts plants, but these impacts can prove to be very beneficial and positive as Molisch stated.


CASE STUDY: Juglone and Melanoma Cancer

There are many studies on juglone and its negative effect on plants. Yet, only a limited amount of research on juglone’s connection to cancer treatment exists. One such study, focusing on methodology, was conducted and led by Aithal (2012). Aithal’s work “...aimed at evaluating the in vitro and in vivo radiosensitizing property of juglone against B16F1 melanoma cells” (2012, p. 69).


Aithal already had a study on “in vitro” radiosensitizing with juglone and concluded that “the cytotoxic potential of juglone was mediated by multifactorial mechanisms involving oxidative stress, cell membrane damage, and clastogenic effect ultimately leading to cell death by both apoptosis and necrosis” (Aithal, 2012, p. 69). This “in vitro” radiosentizing was done using gamma radiation. The amount of space between the source of the radiation to each Swiss albino mouse was 73 cm (Aithal, 2012, p. 70). (Image A).


In Aithal’s new study in 2012 which used “in vivo” radiosensitizing, Aithal knew that juglone was known to suppress mammary tumors in Swiss albino mice, so they were the test subjects in the study (2012, p. 69). The tumor irradiation was carried out in a field size of 10.1 cm x 10.1 cm on each Swiss albino mouse. Each mouse in the “in vivo” experiment was injected with viable melanoma cancer cells in order to grow tumors. Once the tumor size reached 100 + 10 mm^3, the mice were then tested (image B). The mice were put into groups and given different concentrations of juglone: 0, 0.5, 1, and 1.5 mg/kg of body weight (BW) at single doses. The study concluded that higher concentrations of juglone caused greater growth inhibition of the tumor.

In conclusion, higher concentrations of juglone in the radiation therapy proved to eradicate and treat more of the tumors in each mouse. The mice with the highest concentrated dosage (1.5 mg of juglone per kilogram of BW) lived the longest after treatment, compared to the mice who received no juglone-integrated treatment.


Discussion Questions:

  • Should juglone radiosensitizing therapy be tested on humans given the positive results from Aithal’s study?

  • Besides radiation therapy, can juglone be integrated into other cancer treatments?


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