Abstract Arum palaestinum Boiss. Recent work demonstrates anticarcinogenic action both in vitro and in vivo, and that work is coupled with a proof-of-principle mechanism of action data showing induction of the pro-apoptotic protein, caspase Safety data regarding toxicity are encouraging. Acute dosing animal studies and in vitro studies, which compare effects on cancerous and healthy cell lines, show toxicity thus far limited to cancer cells.
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Arum palaestinum is a plant commonly found in the Middle East that is ingested as an herbal remedy to fight cancer. Verified prostate cancer cells were plated as 3D spheroids to determine the effect of extract from boiled Arum Palaestinum Boiss roots.
Control mice 10 mice in each group received vehicle in the same manner and volume. When GZ17 was applied to non-cancer tissue, in this case, human islets, there was no cell death at doses that were toxic to treated cancer cells.
Preliminary toxicity studies were conducted on rats using an up-down design, with no signs of toxic effect at the highest dose. While there was a trend towards lower excised tumor weight at study termination in the GZ17 treatment group, there was no statistical difference. Fortified Arum palaestinum Boiss caused a reduction in live cells within prostate cancer spheroids and blocked tumor growth in xenografted prostate tumors in mice without signs of toxicity.
The use of herbal remedies is widespread in both developing and developed countries [ 1 ]. This type of treatment is vitally important to populations without other healthcare options. In addition, the use of herbals and the subsequent analysis of active ingredients has been important in the formation of many modern drugs.
Wild edible plants have always been an important source of therapeutics in traditional folk medicine. One of the most common plants ingested in the Palestinian region is the Arum palaestinum Boiss [ 3 ], also known as the Black Calla Lily. Often it is boiled and then the leaves are fried in olive oil and eaten because it is believed to protect from colon cancer.
It is also commonly ingested as a tea. In fact, Arum palaestinum Boiss is one of the most commonly utilized plants for cancer patients in the region [ 3 ]. Yet, little is known about its active ingredients or its efficacy as an anticancer agent.
In fact, there is a paucity of published articles devoted to the potential medicinal effects of this plant. Arum palaestinum Boiss is a member of the Araceae family of plants, many of which contain polyphenols, alkaloids, flavone C-glycosides, flavonols, flavones, proantrhocyanidins and polyhydroxy alkalokds [ 4 — 7 ]. The plant is known to contain antioxidant activity [ 4 , 8 ]. Some active compounds have been isolated directly from Arum palaestinum Boiss including two flavone C-glucosides isoorientin and vitexin [ 9 ].
The purpose of this study was to determine whether native Arum palaestinium Boiss and its fortified version had anti-cancer activity against aggressive androgen-independent prostate cancer models in vitro and in vivo.
Arum palaestinum Boiss roots and leaves were collected from wild samples or were cultivated on site. Samples were submitted to the Missouri Botanical Garden, St. The mixture was filtered to remove large particles, resulting in the plant extract that was used in testing.
When working with plant extracts, the exact amount of each chemical component is difficult to control from plant to plant. Chemical components of the extract have been described elsewhere [ 10 ].
To concentrate the elixir for in vitro studies, a powder version was obtained by drying using rotoevaporation, followed by exposure to nitrogen to drive all remaining liquid out of the product, followed by manual pulverization. Prostate cancer cells 22Rv1 are a recognized cell model of androgen-independent prostate cancer [ 11 ].
Methods for fabrication of the micromold and loading cultured cells into the micromold plate have been published previously [ 12 , 13 ]. Prostate cancer spheroids were exposed to increasing doses of the extract of Arum palaestinium Boiss, GZ17 dose range from 0 — 6. Each trial was run with at least four replicates at each dose. At the completion of the exposure time, PrestoBlue Life Technologies, Inc was added to each well and fluorescence read ex.
Results were averaged following background subtraction and normalized to untreated cells. Toxicity studies were conducted on freshly isolated human islets, cultured vascular smooth muscle cells, and cultured fibroblasts. Results were averaged following background subtraction. Four replicates at each concentration were tested along with replicates of media only, and cells plus media only, microliters total volume per well.
Luminescence was read with a plate reader Perkin Elmer, Enspire. Changes in signal for assays were background subtracted and normalized to the 0 drug baseline. Specifically, daily evaluations included skin, fur, eyes, mucous membranes, respiratory rate, and central nervous system behavior.
Particular attention was directed for signs of tremors, convulsions, salivation, diarrhea and coma. Animal distress was monitored daily and no animals showed signs of distress throughout the study.
The immunocompromised mouse model using the androgen independent PC3-MM2 cells has been shown to be one of the most robust models for prostate cancer [ 14 ]. Tumors were allowed to develop to a measurable size prior to the initiation of the treatment with GZ Seven days following the injection of the cancer cells, tumors were visible and baseline tumor measurements were performed.
The tumor size was measured with calipers twice weekly. Twenty mice were divided into treatment and vehicle groups 10 each according to tumor size so that both groups had animals with matched tumor burdens. Animals were monitored twice daily for signs of acute or chronic pain due to the tumor burden and were euthanized by CO 2 asphyxiation along with cervical dislocation. Tumors and organs were dissected, cleaned of fat and connective tissue and weighed.
Prostate cancer spheroids were exposed to increasing doses of Arum palaestinum Boiss extract or to the fortified version of the plant extract called GZ Both showed a dose-dependent increase in cell death at concentrations ranging from 0. IC50 values could not be calculated, as the maximal effect could not be reached with the highest concentration of the pure plant extract due to its precipitation at higher concentrations.
For this reason, the extract was dried to obtain a solid form for reconstitution in water. The effect on prostate cells was more evident using the reconstituted version of GZ17 Fig. It was compared to the vehicle control, which induced no cell death at the same concentrations. Prostate cancer spheroids respond to Arum paleastinum Boiss and the fortified GZ GZ17 was more potent at inducing cell death compared to the plant extract with statistically lower cell numbers at 3.
The additives open circles had little effect on cell viability. The fortifying components added to Arum palaestinum Boiss to create GZ17 were tested alone for any effect on prostate cancer cells. In contrast, when the 3 were combined with the plant to form GZ17, the cell death rate was greatly enhanced to the point that nearly all cells were dead at the highest tested dose.
To determine the method of cell death, activation of caspase proteins were surveyed. While cell death was measured at GZ17 doses of 0. GZ17 induces a dramatic increase in caspase 6 levels. Prostate cancer spheroids were exposed to increasing doses of GZ17 and caspase 6 levels measured. Caspase 6 increased 3 times, beginning at low doses.
GZ17 caused no cell-death on the human islets with cell numbers greatest at the highest doses Fig. Using the same methods, IC 50 levels were determined for GZ17 on non-cancerous vascular smooth muscle cells and fibroblasts.
GZ17 is less toxic on non-cancer human islets. GZ17 failed to induce cell death in the human islets, but consistently caused a dramatic loss of cancer cells. An up and down toxicity design was used to gather preliminary data on in vivo toxicity of the ingested GZ No signs of pain related behavior, respiratory or cardiovascular distress, tremors, convulsions, salivation, diarrhea, or coma were noted.
Skin and fur, eye and mouth mucosa, and central nervous system function were normal. Upon necropsy at the completion of the study, all abdominal and thoracic tissues were normal. The subsequent animal subjects also showed no gross signs of toxicity and no organ abnormality at the time of necropsy.
Having determined that GZ17 contained anti-cancer properties on prostate cancer cells in vitro with no signs of toxicity in rats, the compound was used for complimentary in vivo studies, employing a mouse model of prostate cancer. Prostate cells were injected into all mice to form tumor-like masses prior to treatment with GZ The animals used in this study appeared healthy throughout the treatment.
Mice were weighed twice weekly. There was no difference in body weight between the two groups throughout the study Fig. There was a 6. The difference was not statistically significant and began prior to the initiation of the GZ17 treatment. Animal weight. Mice were weighed prior to treatment with GZ17 or the vehicle. Treatment began on day 0. There was no statistical difference in the body weights of either group of mice throughout the 3-week study.
Tumor sizes were measured twice per week. Prostate tumors grew steadily throughout the 3-week treatment period in the vehicle-treated mice.
GZ17 slowed tumor growth when compared to the vehicle group with only a 9. By day 6 and for all subsequent measurements there was a statistically significant increase in the tumor volume of the vehicle-treated mice. There was no statistically significant increase in tumor size until day 16 in the GZtreated group.
On the day of euthanasia, the average tumor volume was more than double in the controls compared to the treated mice. Furthermore, treated mice showed no changes in behavior, activity levels, grooming or other indications of altered general health.
At completion of the study, the tumors were excised and weighed. Tumor volume. Tumor volume was measured in 3 dimensions with calipers. The size of the tumors and the rate of tumor growth were both statistically greater in the vehicle-treated mice, compared to the GZ In order to assess whether GZ17 caused unintended side effects, organs from all animals in the 3-week treatment study were removed, inspected and weighed.
In agreement with the earlier rat studies, there were no adverse signs of drug effect such as altered gross morphology of the organs analyzed, including indications of metastasis, in the brain, heart, kidneys, liver, lungs, or spleen. Complementary medicine is commonly used among cancer patients. Classical research focusing on a single active compound disregards the historical knowledge of the traditional remedy and the source of the plant.
Arum Palaestinum: An Anticarcinogenic Plant with Promise
We'd like to understand how you use our websites in order to improve them. Register your interest. The Arum palaestinum plant is one of the 26 species of the Arum genus of the Araceae family. This plant species is found through the Mediterranean region, Western Asia, and Europe. The leaves and seeds of the plant contain needle-shaped oxalate crystals that can irritate the affected tissue skin, oral cavity, or GI tract upon exposure. Up to this date, there is no available literature supporting the epidemiology or the clinical manifestations of poisoning by this plant. We extracted demographic data and clinical data from those digital files.
Arum palaestinum is a plant commonly found in the Middle East that is ingested as an herbal remedy to fight cancer. Verified prostate cancer cells were plated as 3D spheroids to determine the effect of extract from boiled Arum Palaestinum Boiss roots. Control mice 10 mice in each group received vehicle in the same manner and volume. When GZ17 was applied to non-cancer tissue, in this case, human islets, there was no cell death at doses that were toxic to treated cancer cells.
Arum palaestinum as a Food-Medicine
Arum palaestinum is a species of flowering herbaceous perennial plant in the family Araceae and the genus Arum also known as black calla , Solomon's lily , priest's hood , noo'ah loof and kardi  It is native to the Levant and other parts of the Mediterranean Basin , and has been naturalized in North America, North Africa, Europe, Western Asia, and Australia    The family Araceae includes other well-known plants such as Anthurium, Caladium , and Philodendron. Arum palaestinum is perhaps best known for it long history in the Middle East as food and for it use in traditional Middle Eastern medicine. It blooms in the spring, between the months of March and April, by which time the plant is easily recognized by its dark purplish-black spadix enclosed by a reddish-brown spathe. The leaves of A. The root is tuberous.
Black Calla Lily is a flowering perennial in the arum family that is native to eastern Mediterranean areas. The trowel-shaped foliage emerges from the tuber in the fall and forms a clump that stays green all winter. It is important to have it in a very well-drained site. In spring the dark purplish-black spadix enclosed in a purplish-black spathe appears.