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Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo

Authors:
  • IDEXX BioResearch, Columbia, United States

Abstract

Prostate cancer is an important public health problem. It is an excellent candidate disease for chemoprevention because prostate cancer is typically slow growing and is usually diagnosed in elderly males. Pygeum africanum (Prunus africana or Rosaceae) is an African prune (plum) tree found in tropical Africa. An extract from the bark of Pygeum africanum has been used in Europe as a prevention and treatment of prostate disorders including benign prostatic hypertrophy (BPH). More recently in the USA, the phytotherapeutic preparations of Pygeum africanum and Saw palmetto have been marketed for prostate health including prostate cancer prevention and treatment. The anti-cancer potential of Pygeum africanum has been tested both in vitro (PC-3 and LNCaP cells) and in vivo (TRAMP mouse model). In tissue culture, ethanolic extracts (30%) of Pygeum africanum inhibited the growth of PC-3 and LNCaP cells; induced apoptosis and altered cell kinetics; down regulated ERalpha and PKC-alpha protein, and demonstrated good binding ability to both mouse uterine estrogen receptors and LNCaP human androgen receptors. TRAMP mice fed Pygeum africanum showed a significant reduction (P = 0.034) in prostate cancer incidence (35%) compared to casein fed mice (62.5%). Pygeum africanum, which is widely used in Europe and USA for treatment of BPH, has a significant role in regulation of prostate cancer both in vitro and in vivo and therefore may be a useful supplement for people at high risk for developing prostate cancer.
... In the last decades, several plants have been confirmed to contain chemo-preventive and therapeutic agents for various cancers [11][12][13][14][15][16][17][18][19][20]. These studies show the effectiveness and synergistic effects of phytochemicals in plant extracts in various diseases [15,21,22]. ...
... Over 60% of currently used anti-cancer agents are estimated to be derived from natural sources, such as plants, marine organisms, and microorganisms [15,17,30,31]. Good examples of plant sources include Prunus africana [15,17], African cherry (Prunus africana (Hook.f.) Kalkman) or Pygeum africanum (Hook. ...
... Over 60% of currently used anti-cancer agents are estimated to be derived from natural sources, such as plants, marine organisms, and microorganisms [15,17,30,31]. Good examples of plant sources include Prunus africana [15,17], African cherry (Prunus africana (Hook.f.) Kalkman) or Pygeum africanum (Hook. f.), bitter almond, African prune, and red. ...
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Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their effects have been linked to phytochemicals such as phenolic compounds and their antioxidant activities. The abundance and complexity of these bio-constituents highlight the need for well-defined in vitro characterization and quantification of the plant extracts/preparations that can translate to in vivo effects and hopefully to clinical use. This review article seeks to provide relevant information about the applicability of cell-based assays in assessing anti-cytotoxicity of phytochemicals considering several traditional and current methods.
... Many scientific studies have confirmed the significant antiprostate cancer effects of P. africana stem bark, whereby its use as an antiprostate cancer agent has in fact already been patented [17]. In an in vivo study, transgenic adenocarcinoma of the mouse prostate (TRAMP) mice fed on P. africana (synonym Pygeum africanum) showed a significant reduction (p � 0.034) in prostate cancer incidence compared with casein-fed mice [18]. Similarly, in an in vitro study, the bark extract of P. africana was observed to induce about 50% growth inhibition of human prostate cancer (PC-3) and also induced significant apoptosis in the PC-3 cell line [18]. ...
... In an in vivo study, transgenic adenocarcinoma of the mouse prostate (TRAMP) mice fed on P. africana (synonym Pygeum africanum) showed a significant reduction (p � 0.034) in prostate cancer incidence compared with casein-fed mice [18]. Similarly, in an in vitro study, the bark extract of P. africana was observed to induce about 50% growth inhibition of human prostate cancer (PC-3) and also induced significant apoptosis in the PC-3 cell line [18]. PC-3 is one of the main cell lines in in vitro studies on human prostate cancer [19]. ...
... In this study, numerous phytochemicals present in P. africana extracts were identified (Table 1), and antiprostate cancer effects of the P. africana samples examined may be associated with some of these compounds. β-Sitosterol is one of the phytochemicals contributing to the antiprostate cancer effects of P. africana [18] and has been observed to induce apoptosis in human prostate cancer cells in cases of prostate lymph-node carcinoma [32,33]. ...
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Prostate cancer is one of the major causes of cancer-related deaths among men globally. Medicinal plants have been explored as alternative treatment options. Herein, we assessed the in vitro cytotoxic effects of 70% ethanolic root extracts of six-month-old micropropagated Prunus africana (PIR) on PC-3 prostate cancer cells as an alternative to the traditionally used P. africana stem-bark extract (PWS) treatment. In vitro assays on PC-3 cells included annexin-V and propidium iodide staining, DAPI staining, and caspase-3 activity analysis through western blotting. PC-3 cells were exposed to PWS and PIR at different concentrations, and dose-dependent antiprostate cancer effects were observed. PC-3 cell viability was determined using CCK-8 assay, which yielded IC 50 values of 52.30 and 82.40 μg/mL for PWS and PIR, respectively. Annexin-V and PI staining showed dose-dependent apoptosis of PC-3 cells. Significant (p < 0.001) percent of DAPI-stained apoptotic PC-3 cells were observed in PWS, PIR, and doxorubicin treatment compared with the negative control. PWS treatment substantially elevated cleaved caspase-3 levels in PC-3 cells compared with the PIR treatment. ese results provide evidence for the antiprostate cancer potential of PIR and sets a basis Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2022, Article ID 8232851, 12 pages https://doi.org/10.1155/2022/8232851 for further research to enhance future utilization of roots of young micropropagated P. africana for prostate cancer treatment as an alternative to stem bark. Moreover, micropropagation approach may help provide the required raw materials and hence reduce the demand for P. africana from endangered wild population.
... Generally, phytonutrients are desirable in food consumption for health benefits. Phytosterols have been proven scientifically to reduce low-density lipoprotein LDL and total cholesterol TC levels 34 , induce apoptosis in prostate 35 , breast 36 and colon 37 cancer cells, interrupt testosterone metabolism 38 , and inhibit inflammation 39 . Likewise, carotenoids possess anti-inflammatory, antioxidant and anticancer activities 40 , as well as decreasing the risk of age-related macular degeneration and cataracts 41 . ...
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Oxidative stress occurs due to the imbalance amount of the free radicals and antioxidants in human body which often associated with numerous chronic diseases. The antioxidant properties of red palm-pressed mesocarp olein (PPMO) have not been widely studied. Therefore, antioxidant properties of PPMO relative to commercially available edible oils, namely red palm olein (RPO), palm olein (PO), extra virgin olive oil (OO) and extra virgin coconut oil (CNO) were studied. PPMO exhibited significant higher phytonutrients which more than 2-fold compared to the edible oils. Overall, antioxidant screening indicated that PPMO has significantly higher antioxidant activities than RPO, PO and CNO in term of DPPH, H2O2, NO scavenging and FIC; and significantly higher H2O2 and FIC than OO. The outcomes of this study reveal that PPMO is as good as commercially available edible oil, also a good source for food applications and dietary nutritional supplements. More importantly, the utilization of PPMO could mitigate oil palm waste problem and results in positive environmental impact. graphical abstract Fullsize Image
... Rettig et al. (2008) showed that the extract of pomegranate results in the inhibition of the growth of androgen-independent PCa via a nuclear factor-KB-dependent mechanism. Shenouda et al. (2007) showed that an extract from the bark of an African plum tree, Pygeum africanum, inhibited the proliferation of PC-3 and LNCaP cells and induced apoptosis via downregulation of ERa and PKCa protein, which displayed a virtuous binding ability to both LNCaP human ARs and mouse uterine estrogen receptors. ...
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... Rettig et al. (2008) showed that the extract of pomegranate results in the inhibition of the growth of androgen-independent PCa via a nuclear factor-KB-dependent mechanism. Shenouda et al. (2007) showed that an extract from the bark of an African plum tree, Pygeum africanum, inhibited the proliferation of PC-3 and LNCaP cells and induced apoptosis via downregulation of ERa and PKCa protein, which displayed a virtuous binding ability to both LNCaP human ARs and mouse uterine estrogen receptors. ...
Article
Full-text available
Prostate cancer is the most common type of cancer among men and the second most frequent cause of cancer-related mortality around the world. The progression of advanced prostate cancer to castration-resistant prostate cancer (CRPC) plays a major role in disease-associated morbidity and mortality, posing a significant therapeutic challenge. Resistance has been associated with the activation of androgen receptors via several mechanisms, including alternative dehydroepiandrosterone biosynthetic pathways, other androgen receptor activator molecules, oncogenes, and carcinogenic signaling pathways. Tumor microenvironment plays a critical role not only in the cancer progression but also in the drug resistance. Numerous natural products have shown major potential against particular or multiple resistance pathways as shown by in vitro and in vivo studies. However, their efficacy in clinical trials has been undermined by their unfavorable pharmacological properties (hydrophobic molecules, instability, low pharmacokinetic profile, poor water solubility, and high excretion rate). Nanoparticle formulations can provide a way out of the stalemate, employing targeted drug delivery, improved pharmacokinetic drug profile, and transportation of diagnostic and therapeutic agents via otherwise impermeable biological barriers. This review compiles the available evidence regarding the use of natural products for the management of CRPC with a focus on nanoparticle formulations. PubMed and Google Scholar search engines were used for preclinical studies, while ClinicalTrials.gov and PubMed were searched for clinical studies. The results of our study suggest the efficacy of natural compounds such as curcumin, resveratrol, apigenin, quercetin, fisetin, luteolin, kaempferol, genistein, berberine, ursolic acid, eugenol, gingerol, and ellagic acid against several mechanisms leading to castration resistance in preclinical studies, but fail to set the disease under Frontiers in Cell and Developmental Biology | www.frontiersin.org 1 November 2021 | Volume 9 | Article 745177 Singla et al. Natural Products Against CRPC control in clinical studies. Nanoparticle formulations of curcumin and quercetin seem to increase their potential in clinical settings. Using nanoparticles based on betulinic acid, capsaicin, sintokamide A, niphatenones A and B, as well as atraric acid seems promising but needs to be verified with preclinical and clinical studies.
... In the last decades, a considerable number of plants has been shown to possess chemo-preventive and therapeutic properties against various cancers [1,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28], with the US National Cancer Institute reporting reproducible anticancer properties for about 3000 plants out of a total of 35,000 plant species screened for potential anticancer activities [29]. These studies show the effectiveness and synergistic effects of phytochemicals in plant extracts in various diseases [19,30,31]. ...
Preprint
This review article seeks to provide relevant information about the applicability of cell-based assays in assessing cytotoxicity of phytochemicals in light of several traditional methods available. Phenolic compounds and other phytochemicals are significant resources for drug discovery and development, thus underlining the enormous potentials of plant-derived natural products for the prevention and management of oxidative stress associated with cancer and other diseases. These effects have been linked to the content of phytochemicals such as phenolic compounds and their antioxidant properties. The abundance and complexity of these bio-constituents highlight the need for well-defined methods for the in vitro characterization and quantification of extracts and/or preparations that can translate to in vivo effects. Cell culture systems provide a useful model for basic research and a wide range of clinical in vitro studies and physiological processes as well as assessing the toxicity and therapeutic potential of compounds including plant extracts with potential medicinal benefits. Their use in cancer research provide a useful insight into possible therapeutic properties of phytochemicals at the cellular level. This approach has been instrumental in the initial stages of developing chemotherapeutic agents where human cancer cell lines are used as experimental models. These models have continued to contribute to elucidating specific requirements for certain biochemical events associated with proliferation, metabolism, loss of cell viability/apoptosis. Cell culture systems remain a promising tool in natural product development.
... 11,12 They have also shown to be effective in weight control because of the increasing effect of lipolysis, and have positive effect on the colon and prostate cancer by preventing the formation of malignant tumour development. 13 In recent years, due to its important role in the human diet, the sterol content of the beebread has gained importance. Therefore, the aim of this study is to determine sterol contents of beebread samp les from different geographical and botanical origin. ...
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Chapter
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The efficacy of an extract of Pygeum africanum in the treatment of micturitional disorders due to benign prostatic hyperplasia was tested in a multicentre double-blind trial versus placebo. Capsules containing 50 mg of Pygeum africanum extract or placebo were administered at a dosage of 1 capsule in the morning and 1 capsule in the evening over aperiod of 60 days. 263 patients were included in this study, which was carried out in 8 centres in Germany, France, and Austria. Evaluation was mainly based on quantitative parameters such as residual urine, uroflowmetry and the precise monitoring of diurnal and nocturnal pollakiuria. Treatment with the Pygeum africanum extract led to a marked clinical improvement: a comparison of the quantitative parameters showed a significant difference between the Pygeum africanum group and the placebo group with respect to therapeutic response. The characteristic subjective symptoms of micturitional disorders, which were evaluated by the patients in a qualitative manner, were also significantly improved by administration of Pygeum africanum extract. Overall assessment at the end of therapy, showed that micturition improved in 66% of the patients treated with Pygeum africanum extract, as compared with an improvement of 31% in the placebo group. The difference was significant at the statistical level of p < 0.001. During therapy with Pygeum africanum extract, gastrointestinal side effect occurred in 5 patients. Treatment was discontinued in three of those cases.
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Zusammenfassung Trotz traditioneller Popularität als Arzneimittel in vielen Ländern Europas und trotz wachsender Beliebtheit als “Nahrungsmittelzusatz” in den USA bleibt die Rolle der Phytotherapie für LUTS (Lower Urinary Tract Symptoms) und benigner Prostatahyperplasie (BPH) umstritten. Legt man evidenzbasierte Kriterien an, zeigen nur wenige randomisierte Studien ohne ausreichend langes Follow-up sowie einige Metaanalysen vornehmlich über Serenoa repens und Pygeum Africanum sowie jüngste Studien mit Kürbiskernen einen klinischen Effekt bei guter Verträglichkeit. Umso mehr sind randomisierte, placebokontrollierte Studien erforderlich, um die tatsächliche therapeutische Potenz der einzelnen Präparate einzuordnen.
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The efficacy of an extract of Pygeum africanum in the treatment of micturitional disorders due to benign prostatic hyperplasia was tested in a multicentre double-blind trial versus placebo. Capsules containing 50 mg of Pygeum africanum extract or placebo were administered at a dosage of 1 capsule in the morning and 1 capsule in the evening over a period of 60 days. 263 patients were included in this study, which was carried out in 8 centres in Germany, France, and Austria. Evaluation was mainly based on quantitative parameters such as residual urine, uroflowmetry and the precise monitoring of diurnal and nocturnal pollakiuria. Treatment with the Pygeum africanum extract led to a marked clinical improvement: a comparison of the quantitative parameters showed a significant difference between the Pygeum africanum group and the placebo group with respect to therapeutic response. The characteristic subjective symptoms of micturitional disorders, which were evaluated by the patients in a qualitative manner, were also significantly improved by administration of Pygeum africanum extract. Overall assessment at the end of therapy, showed that micturition improved in 66% of the patients treated with Pygeum africanum extract, as compared with an improvement of 31% in the placebo group. The difference was significant at the statistical level of p less than 0.001. During therapy with Pygeum africanum extract, gastrointestinal side effects occurred in 5 patients. Treatment was discontinued in three of those cases.
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This clinical study has been designed to evaluate the efficacy of an extract of Pygeum Africanum (Tadenan) (Roussel-Pharma) in patients suffering from prostatic hypertrophy or chronic prostatitis. The drug has been administrated to 18 patients, for 60 days, as double of standard dosage (200 mg/die per os, instead of 100 mg/die). Because of the high frequency of association of sexual disorders with those two pathologies, we have extended the study also to sexual disorders selecting patients suffering from prostatic hypertrophy or chronic prostatitis and, simultaneously, from sexual disturbances. No side effects have been observed during the treatment. The urinary disturbances have been evaluated by anamnesis and prostatic transrectal echography; sexual disorders have been evaluated by anamnesis and nocturnal penile tumescence and rigidity (NPTR) monitoring. Furthermore, dosage of serum levels of the hormones LH, FSH, Prolactin, 17 beta-Estradiol and Testosterone has been performed before and after therapy. Pygeum Africanum extract administration improved all the urinary parameters we investigated; prostatic echography relieved reduction of peri-urethral edema. Also an improvement of sexual behaviour has been obtained; but we have not found significant differences between serum hormonal levels before and after therapy, as well as for NPTR.
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Two random groups of sixty patients each were given an extract of pygeum africanum in one group, and a placebo in the other. The results highlight the placebo effect (50 per cent of cases), and that the extract provided an overall improvement in the functional symptoms. The differences between the two treatments were statistically significant for nocturnal frequency, difficulty in starting micturition, and incomplete emptying of the bladder.