Breadfruit extracts receive patent for treating prostate cancer

African breadfruit (Treculia africana,inset are the seeds

• Nigerian, Korean scientists make breakthrough as local plant inhibits tumour growth in humans
Until now, it is better known for its seeds, which are used in making beverages and porridge meals. Earlier studies had suggested that eating meals rich in breadfruit could be a better option to sleeping pills in inducing sleep and treating mentally ill patients. But recent researches indicate that extracts of breadfruit provide novel treatment for prostate cancer. CHUKWUMA MUANYA writes.

A composition of breadfruit (Artocarpus altilis), containing extracts of fruits, leaves, or stems, or fractions thereof as active ingredients has received patent for preventing or treating cancer.

Botanically called Artocarpus altilis, breadfruit is a species of flowering tree in the mulberry family Moraceae.
The African breadfruit is botanically called Treculia africana. It is a tropical tree crop also belonging to the taxonomic family Moraceae. It is also called wild jackfruit or African-boxwood. In Nigeria, it is called ukwa in Ibo. It is afon in Yoruba; ize in Benin, Jekri and Sobo; izea in Ijaw; and ediang in Efik.

The abstract of the Patent EP 2889038 A1 noted: “The present invention relates to a pharmaceutical composition for preventing and treating cancer which comprises the extracts of Artocarpus altilis fruits, leaves, or stems, or the fractions thereof as active ingredients. The extracts of Artocarpus altilis fruits, leaves, or stems, or the fractions thereof, according to the present invention, suppress the activity of signal transducer and activator of transcription (STAT3) which plays an important role in the growth of a cancer cell line and in the immune function of the human body, and can thus be effectively used in the prevention and treatment of cancers such as colorectal cancer, stomach cancer, prostate cancer, breast cancer, renal cancer, liver cancer, brain tumor, lung cancer, uterine cancer, colorectal cancer, bladder cancer, or pancreatic cancer.”

The patent filled on July 26, 2013, was published on July 1, 2015.
The inventors are Byoung-Mog Kwon, Dong Cho Han, Joongku Lee, Yoon-jeong JEON, and Sang Ho Choi while the applicant is the Korea Research Institute of Bioscience and Biotechnology.

The patent is the brain child of a novel research by a team of researchers from National Biotechnology Development Agency (NABDA), Abuja; Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, South Korea; Center for Biocomputing and Drug Development, Adekunle Ajasin University, Akungba-Akoko; and the Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Oyo State.

The team made a breakthrough in prostate cancer treatment by discovering the active principle in the extract of breadfruit and elucidating the molecular target in tumor cells.

In the study, published in May, 2015 in the journal Phytochemical Research, NABDA’s Director for Genomics and Bioinformatics, Prof. Oyekanmi Nash and his colleagues showed that the partially purified fraction from the plant, and the isolated geranyl dihydrochalcone, CG901, down-regulated the expression of STAT3 target genes, induced apoptosis in DU145 prostate cancer cells via caspase-3 and PARP degradation, and inhibited tumor growth in human prostate tumor (DU145) xenograft initiation model.

These results suggest that Artocarpus altilis could be a good natural source and that the isolated compound will be a potential lead molecule for developing novel therapeutics against STAT3-related diseases, including cancer and inflammation.

On the industrial applicability of the discovery, the patent noted: “As mentioned above, the present invention to can be effectively used a pharmaceutical composition for prevention and treatment of cancers selected from the group consisting of colorectal cancer, stomach cancer, prostate cancer, breast cancer, renal cancer, liver cancer, brain tumor, lung cancer, uterine cancer, colon cancer, bladder cancer, and pancreatic cancer, wherein the comprises the extracts of Artocarpus altilis fruits, leaves, or stems, or the fractions thereof as active ingredients.”

Nash said: “It is important to know that more than 50 per cent of currently prescribed drugs are originated from natural products or their derivatives, and an important goal in antitumor drug discovery is the identification of compounds with selective toxicity toward cancer cells. Herbal medicines, as an important novel source with a wide range of pharmaceutical potential, are being used to treat human ailments including almost all types of cancer.

Therefore, we are interested in herbal medicines with low toxicity against normal human cells, and we screened (over 4000) natural compounds, isolated from herbal medicines, to find STAT3 inhibitors. Through this screen, we found A. altilis extracts, its partially purified fraction, and the isolated CG-901 as inhibitor of STAT3 activation. Our mechanistic study indicated that extracts inhibited the activation of STAT3 signaling by interfering with STAT3 phosphorylation

One of the aims in this study was to isolate active compounds from herbal medicines and investigate the effects of the compounds on the STAT3 signaling pathway, its gene products, and cellular responses. Here, we isolated CG901 as a STAT inhibitor from A. altilis extracts, and we also found that CG-901 suppressed constitutive STAT3 activation in human prostate cancer cell line (DU145) in a dose- and time-dependent manner.

Moreover, CG-901 also down regulated the expression of STAT3-regulated gene products, including Mcl-1, cyclin A, and surviving and selectively inhibited the growth of STAT3- activated cells (DU145). This is the first report of a geranyl chalcone showing a potent STAT3-inhibiting activity and inhibiting tumor growth in the mice xenografted with DU145 cells. Our results suggest that CG-901 might be a potential lead molecule for developing novel therapeutics against STAT3-activated human tumors.

In a subsequent study, published in the November, 2015 edition of the Journal of Molecular Modeling, Nash led a team of computational Biologists at the Center for Biocomputing and Drug Development, Adekunle Ajasin University, Akungba-Akoko, including Dr. Omotuyi Olaposi to deploy Computational techniques to identify the CG-901 target upstream of STAT3 signaling. In this study, CG-901scaffold was identified as a robust Janus Kinases inhibitor targeting JH1 catalytic domain of the enzyme and disrupting catalytic communication within the enzyme, comparable with synthetic inhibitors currently known for the enzymes.

Director General (DG)/Chief Executive Officer (CEO of the NABDA Prof. Lucy Ogbadu, the explained that the findings from the computational studies now avail the researchers the opportunity to rationally redesign CG-901 chalcone scaffold, a key step that might provide far-fetched solution to the global scourge of prostate cancer from the stable of African scientists like Nash.

African breadfruit and chronic diseases
Also, African breadfruit extracts may provide next sleeping pill. Nigerian researchers have found that extracts of African breadfruit (Treculia africana) could be the next best natural sedative without side effects, thereby making it useful in the treatment of mental illness.
Sleeplessness or rather insomnia has been linked with the rising cases of degenerative diseases such as diabetes, obesity, heart diseases and cancer.

Little wonder the sleeping pill market is experiencing a boom.
However, sleeping pills have potentially harmful side effects, including diarrhoea, constipation, dizziness, and parasomnias. Parasomnias are behaviours and actions over which people have no control, like sleepwalking.

The researchers from the Faculties of Pharmacy Niger Delta University, Bayelsa State and Obafemi Awolowo University, Ile-Ife, Osun State found that the crude extract possessed sedative effects, which may be through increase in the activity of GABA in the brain.

GABA is gama amino butyric acid, and is an inhibitory neurotransmitter that is essential for the proper functioning of the brain and the central nervous system, and has the effect of reducing excessive brain activity and promoting a state of calm.
The study published in Ethnobotanical Leaflets is entitled “Central Nervous System Depressant Properties of Treculia africana Decne.”

Nigerian foodstuffs stop prostate cancer
Nigerian researchers have also identified foodstuffs with prostate cancer chemo-preventive polyphenols. The study was published in

Infectious Agent Cancer by Sunday Eneojo.
The study noted: “Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-ὰ-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit (local pear), Moringa oleifera and Syzygium aromaticum (cloves) contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives.

Also black olive or African elemi (Canarium schweinfurthii Engl) oil contained ten phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol.

In addition, tomatoes (Lycopersicon esculentum) which contains the powerful antioxidant and anti-prostate cancer agent, lycopene; cabbage (Brassica oleracea) containing indole-3-carbinol; citrus fruits containing pectin; Soursop (Annona muricata) containing annonaceous acetogenins; soya beans (Glycine max) containing isoflavones; chilli pepper (Capsicum annuum) containing capsaicin, and green tea (Camellia sinensis) containing (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate which are widely reported to posses prostate cancer chemopreventive compounds are also grown in Nigeria and other African countries.

Thus, the high incidence of prostate cancer among males of African extraction can be dramatically reduced, and the age of onset drastically increased, if the population at risk consumes the right kinds of foods in the right proportion, beginning early in life, especially as prostate cancer has a latency period of about 50 years.

Scent leaf inhibits prostate cancer growth
Researchers have also shown the efficacy scent leaf (Ocimum gratissimum) in stopping prostate cancer. The study, titled “Fractionated Ocimum gratissimum Leaf Extract Inhibit Prostate Cancer (PC3·AR) Cells Growth by Reducing Androgen Receptor and Survivin Levels,” was published in the Journal of Health Care for the Poor and Underserved.

In this study, the anti-proliferative activity of the organic solvent-soluble and aqueous extracts of Ocimum gratissimum leaf against the prostate cancer cells PC3·AR were evaluated by their inhibitory effects on the Androgen Receptor (AR) and Survivin protein. Two organic solvent-soluble extracts P2 and P3–2, and a water- soluble extract, PS/PT1, were found to reduce AR and Survivin levels in a time-dependent manner.

In addition, extract PS/PT1, also exhibited the inhibitory activity in a dose-dependent manner. This is the first time that the inhibitory effects of O. gratissimum extracts have been evaluated on the Androgen Receptor (AR) and Survivin protein. The results encouraged the further studies of O. gratissimum as a potential treatment of prostate cancer.
Pygeum africanum and Urtica dioica improve urinary function in enlarged prostate
Scientists have also identified more natural recipes for ameliorating mild to moderate lower urinary tract symptoms (LUTS) in men with enlarged prostate.

Top on the list are plant extracts of Pygeum africanum and Urtica dioica.
Pygeum africanum (African plum tree or bitter almond) is called emi or olowomefa in Yoruba, ka’danya in Hausa and osisi in Ibo.
Commonly called nettle, big string nettle, common nettle, stinging nettle, Urtica dioica is a leafy plant found in most parts of Nigeria, but ubiquitous in the Southern parts. The Igbos call it agbara or akuwa; and it is named osokporode in Urhobo while to the Yorubas, it is ewe esinsin or esisi.

Pygeum africanum has been shown to be beneficial in treating BPH. Benign prostatic hyperplasia (BPH), also known as benign prostatic hypertrophy, is a noncancerous enlargement of the prostate gland. It is especially helpful in increasing urinary function, often limited due to enlarged prostate. Historically, the bark was powdered and used to make a tea, which was taken by mouth for urinary problems.

Moreover, a combination of African plum tree with stinging nettle was found to increase the effectiveness of each herb in improving urinary flow rate.

A new study to evaluate the effect of a combined extract of Urtica dioica and Pygeum africanum on Lower Urinary Tract Symptoms (LUTS) in Nigerian men recorded a 69.1 per cent improvement in symptoms of BPH. The men were placed on the extract African plum tree and stinging nettle in the preparation form of Prostatonin© over nine months (January 2009 to September 2009).

When the scientists reviewed the International Prostate Symptom Score (IPSS) and the Postvoidal Residual Urine Volume (PVR) of the 107 patients that participated in the study, they found that 74 patients showed an improvement in their symptoms while 33 patients did not notice any improvement in their symptoms. However, no patient recorded worsening symptoms.
In addition, the scientists reported no sexually related side effects with the use of the combination of African plum tree with stinging nettle.

The scientists wrote: “Though our evaluation was retrospective and patient population small, we did document some objective improvement in the IPSS of more than half of our patients. These were, however, patients with mild to moderate symptoms. There was also an improvement in the PVR in a sizeable number of patients.

Although it could be argued that these patients with mild to moderate symptoms could be managed by watchful waiting, we think Urtica dioica and Pygeum africanum in the preparation form of Prostatonin© could be a useful option in those patients who desire some form of treatment devoid of any significant general or sexually-related side-effects.

According to them, “although this study cannot be regarded as entirely conclusive, further randomized prospective clinical trials would be required. We believe that the preparation of plant extracts of Pygeum africanum and Urtica dioica has a potential role in the treatment of some patients with mild to moderate LUTS from BPH.”
The 2012 study entitled: “Effect Of The Plant Extracts Pygeum africanum and Urtica dioica on Lower Urinary Tract Symptoms due To Benign Prostatic Hyperplasia in Nigerian Men “was published in The Internet Journal of Urology.

The researchers included O.A Omisanjo, S.O Ikuerowo, E.B Izuagba, J.O Esho and O.A Adegboyega, all from the Lagos State University College of Medicine, Ikeja.
Previous studies on Pygeum africanum postulated that the extracts contained phytosterols and long chain fatty alcohols. Although the exact mechanism of action of the plant is unknown, its analysis suggests it modestly improves urinary flow rates.

Also, several studies, including clinical trials at Lagos University Teaching Hospital (LASUTH), Ikeja have shown that a combination of Pygeum africanum (African plum tree or bitter almond) with saw palmetto (Serenoa repens) significantly reduces urinary hesitancy, urinary frequency, the number of times patients need to wake up at night to urinate and pain with urination in men who experience mild-to-moderate symptoms.

Pygeum has also shown promise in preventing combating and reducing the symptoms of prostate cancer and chronic prostates. In animal studies, pygeum showed an increase in the volume and viability of sperm in the semen. This indicates a possible use of this herb for treating male infertility.
Traditionally, the bark of the tree was gathered and powdered and made into a tea, which was taken for genito-urinary complaints.

Some of the less researched traditional uses of pygeum include use as an aphrodisiac, fever, impotence, kidney disease, malaria, hair loss, partial bladder outlet obstruction (BOO), sexual performance, urinary tract infections, inflammation, malaria, prostatic adenoma, prostatitis and psychosis.
More recently in the United States (US), the phytotherapeutic preparations of Pygeum africanum and Saw palmetto have been marketed for prostate health including prostate cancer prevention and treatment.