Prostate Cancer: Rauwolfia Vomitoria and Pao Pereira

The research on PROSTATE CANCER, PSA, and BPH

Prostate cancer is the most common cancer in men of all races and is the second leading cause of cancer-related death among all men. Traditional medicine provides several well-known options for treatment that are associated with various negative side effects. This has prompted many men to try alternatives, including herbal, treatments.

Dr. Aaron Katz, when Director of the Department of Holistic Urology at Columbia University Medical Center, learned of this interest in alternative approaches to prostate health and decided to study the most promising natural products in his own laboratory using rigorous scientific methods. He tested the anti-prostate cancer effects of the Pao pereira and Rauwolfia vomitoria plant extracts in cell cultures and then in animals carrying human prostate cancers.

The results demonstrated that both the Pao pereira and Rauwolfia vomitoria extracts inhibited the growth of prostate cancer cells in the laboratory and reduced the volume of prostate tumors in mice.  In addition to their anti-prostate cancer activity, Katz also found evidence that a combination of the two extracts has anti-inflammatory effects—lowering PSA in men with elevated levels and reducing the urinary symptoms in men with benign prostatic hyperplasia (BPH).

Prostate cancer is a problematic human disease whose burden to health in the United States could be decreased by a suitable preventive agent or treatment, especially one that might be used as a nutritional supplement.

Our Partners for those publications:

The Center for Integrative Urology and Holistic Medicine in the Department of Urology, Columbia University Medical Center offers the best of complementary and integrative medicine to men and women with genitourinary tract disorders and to all patients seeking healthy, holistic and multidisciplinary approaches to treating various conditions and maintaining wellness. The Center was founded by Jillian L Capodice in 2011.

The mission of the Center for Integrative Urology and Holistic Medicine is to care for the entire person by utilizing safe, evidence-based and individualized treatment approaches. They offer holistic therapies aimed at treating the whole person – body, mind and spirit.

Learn more about Columbia University Medical Center

Nanjing University (NJU or NU, simplified Chinese: 南京大学; traditional Chinese: 南京大學; pinyin: Nánjīng Dàxué; colloquially 南大, Nándà), or Nanking University, is one of the oldest and most prestigious institutions of higher learning in China.

Learn more about Nanjing University

Dr. Katz is an internationally recognized leader in the field of minimally invasive therapies for prostate cancer. He is an advocate of, and practices, integrative medicine, which combines the best scientific advances of conventional medicine with traditional and scientifically validated alternative therapies.

(source: http://www.winthrop.org/departments/specialtycenters/urology/Clinical-Staff/?aaron-katz)

Our Publications

  • Publication on Pao pereira Reducing BPH

    Publication BPH Pao Banner

    May 2020 – “Pao Pereira Extract Suppresses Benign Prostatic Hyperplasia by Inhibiting Inflammation-Associated NFκB Signaling”

    by Yu Dong, Jiakuan Liu, Zesheng Xue, Jingya Sun, Zhengnan Huang, Yifeng Jing, Bangmin Han, Bing Shen, Jun Yan and Ruimin Huang
    BMC Complement Med Ther 20, 150 (2020). https://doi.org/10.1186/s12906-020-02943-2

    Nanjing_University

    Pao pereira extract reduces inflammation in BPH by inhibiting NFKappaB signaling.

    Pao pereira (Pau pereira) is incredibly effective for chronic inflammation of the prostate commonly known as BPH or Benign Prostatic Hyperplasia. BPH is an enlargement of the prostate caused by inflammation that is common among older men. The enlarged prostate gives rise to serious urinary problems and quality of life issues.   

    A new study from Dr. Jun Yan’s group at Nanjing University in China shows that Pao pereira (Pau pereira) inhibits the control center that is activated in prostate inflammation. In BPH, this master switch, called NFKappaB, is turned on which triggers expression of pro-inflammatory cytokines and genes involved in extracellular matrix remodeling. These cytokines trigger proliferation of prostate cells and further enlargement of the gland. The Pao pereira (Pau pereira) extract turns the switch off so NFKappaB signaling is quieted and the levels of cytokines and remodelers are diminished.

    Not only does the extract resolve the inflammatory response in BPH it also reduces viability of the two major cell types in the prostate: epithelial and stromal cells. The chronic inflammation associated with BPH damages and destabilizes the DNA in the cells which renders them susceptible to apoptosis induced by the Pao pereira (Pau pereira) extract.  Apoptosis, or programmed cell death, is triggered in both epithelial and stromal cells in the BPH tissue.

    Induction of apoptosis is the precise mechanism of action of the Pao extract in cancer cells which, as Dr. Beljanksi showed, contain destabilized DNA. Malins’ work revealed that cells in the BPH prostate suffer similar DNA damage even though the cells are not cancerous, but rather chronically inflamed or precancerous. The new study from Dr. Yan’s group shows that DNA damage in BPH is sufficient to result in apoptosis in the presence of the Pao pereira (Pau pereira) extract.

    There is more!

    A previous paper from the Nanjing group showed that Pao pereira (Pau pereira) addresses the androgen imbalance that promotes BPH as men age (read the previous study from the Nanjing group here). The extract inhibits the enzyme that converts testosterone to dihydrotestosterone which triggers prostate enlargement. The Pao extract reduces the size of BPH prostates, lowers the levels of androgen receptor, and lowers PSA–the well-known marker for prostate inflammation. The Pao extract does all of this just as well Finasteride, but without the negative side effects associated with this drug.

    Pao pereira (Pau pereira) is indeed incredibly effective for BPH.

    Abstract

    BPH Publication May 2020

    Background

    Our previous study revealed the extract from the bark of an Amazonian tree Pao pereira (Pau pereira) can suppress benign prostatic hyperplasia (BPH) in a rat model. Herein, we examined its inhibitory effects on human BPH cells and dissect its molecular mechanism.

    Methods

    We applied the Pao extract to human BPH epithelial BPH-1 and prostate myofibroblast WPMY-1 cells. Cell viability, apoptosis and immunoblotting were performed, followed by gene expression profiling and gene set enrichment analysis (GSEA) to detect the differentially expressed genes and signaling pathway induced by Pao extract. Human ex vivo BPH explant organ culture was also used to examine the effects of Pao extract on human BPH tissues.

    Results

    Pao extract treatment inhibited viability and induced apoptosis in human BPH-1 and WPMY-1 cells. Gene expression profiling and the following validation indicated that the expression levels of pro-apoptotic genes (eg. PCDC4, CHOP and FBXO32) were induced by Pao extract in both two cell lines. GSEA further revealed that Pao extract treatment was negatively associated with the activation of NFκB signaling. Pao extract suppressed the transcriptional activity of NFκB and down-regulated its target genes involved in inflammation (CXCL5, CXCL6 and CXCL12) and extracellular matrix (ECM) remodeling (HAS2, TNC and MMP13) in both cultured cells and human ex vivo BPH explants.

    Conclusion

    In both BPH epithelial and stromal cells, Pao extract induces apoptosis by upregulating the pro-apoptotic genes and inhibiting the inflammation-associated NFκB signaling via reducing phosphorylation of NFκB subunit RelA. Our data suggest that Pao extract may be a promising phytotherapeutic agent for BPH.

    Research Publication Data

    BPH Publication Fig 1

    Figure 1 shows Pao pereira (Pau pereira) inhibited the proliferation and induced apoptosis in BPH-1 and WPMY-1 cells. Image a shows changes of BPH-1 and WPMY-1 cells upon Pao extract treated for 48 h. Image b shows the effects of Pao pereira (Pau pereira) on cell viability by the SRB assay. 

    BPH Publication Fig 2

    Figure 2 shows Pao pereira (Pau pereira) induced apoptosis in BPH-1 and WPMY-1 cells. Image a shows the flow cytometry analysis on BPH-1 and WPMY-1 cells treated with Pao pereira (Pau pereira) using an Annexin V-FITC/PI double staining kit. Image b shows the cell death rates in BPH-1 and WPMY-1 cells treated with Pao pereira (Pau pereira). Annexin V-positive cells were defined as apoptotic cells. Image c is the effects of Pao pereira (Pau pereira) on the apoptosis-related proteins by Western blotting assay. Data are presented as mean ± SD; * p < 0.05, ** p < 0.01, and *** p < 0.001

    BPH Publication

    Figure 3 shows Pao pereira (Pau pereira) inhibited NFκB signaling pathway in human BPH tissues. Image a is a schematic diagram of the ex vivo BPH explant culture process. BPH explants were treated with 0, 250, 500 μg/ml Pao pereira (Pau pereira) for 48 h. Image b is the phosphorylation of RelA and protein expression levels of pro-apoptotic and inflammation-associated genes survival-associated proteins (PDCD4 and DDIT3/CHOP) were analyzed by Western blotting in BPH explants with Pao pereira (Pau pereira) treatment. Image c is the mRNA expression levels of target genes from NFκB signaling pathway, pro-apoptotic and inflammation-associated genes in BPH explants with Pao pereira (Pau pereira) treatment by qRT-PCR. * p < 0.05, ** p < 0.01, *** p < 0.001, and ns p ≥ 0.05

    Download Pao Pereira extract suppresses benign prostatic hyperplasia by inhibiting inflammation-associated NFκB signaling

    Click here for more information about Pao pereira and prostate cancer

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  • Publication on Pao pereira Reducing BPH

    December 2019 – “Pao Pereira Extract Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by inhibiting 5α-Reductase”

    by Jiakuan Liu, Tian Fang, Meiqian Li, Yuting Song, Junzun Li, Zesheng Xue, Jiaxuan Li, Dandan Bu, Wei Liu, Qinghe Zeng, Yidan Zhang, Shifeng Yun, Ruimin Huang & Jun Yan
    Scientific Reports 9, 19703 (2019). Doi: 10.1038/s41598-019-56145-z. E pub Dec 23 2019

    Nanjing_University

    BPH (Benign Prostatic Hyperplasia) is so common and discussion about its causes is so frequent that we could well expect there to be good options for shrinking prostates back to normal size and restoring normal urination and prostate health. The usual options for BPH treatment are several widely prescribed drugs that work to reduce prostate size but are also associated with a variety of unpleasant side effects. New research shows that the Pao pereira plant extract, famous for its broad-spectrum anti-cancer effect, is an excellent BPH treatment — as good as the drugs — and it doesn’t induce negative side effects. The study was conducted at Nanjing University under the direction of Dr. Jun Yan.

    The key is a newly discovered modulating effect of the Pao extract on enzymatic pathways that promote the development of BPH. The new paper is entitled “Pao Pereira Extract Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Regulating 5a-reductase”. The critical enzyme pathway is 5a-reductase which converts testosterone to dihydrotestosterone (DHT)—a more active hormone that triggers the proliferation of prostate cells that leads to BPH. By lowering the level of 5alpha-reductase the Pao extract lowers the level of DHT thus removing the trigger for BPH.

    The study confirms that the Pao extract suppresses inflammation of the prostate by affecting the hormone imbalance that occurs in older men as testosterone levels drop and 5a-reductase increases the level of DHT. The extract is also effective at halting the overgrowth of BPH cells in the prostate by inducing cell cycle arrest. It also lowers the level of androgen receptor that mediates hormonal induction of BPH and reduces the level of PSA, the well-known marker for prostate inflammation and cancer. And referring to cancer, by lowering prostate inflammation Pao pereira extract lowers the risk of progression to prostate cancer.

    The experiments were conducted both in vitro and in vivo and no evidence for side effects were seen. The data indicates that the Pao pereira extract provides an ideal therapeutic response for BPH that can be taken without concern for negative side effects. This new work, together with previous research, shows that Pao pereira is effective against all stages of prostate health problems including chronic inflammation, prostate cancer and advanced prostate cancer.

    Abstract

    Scientific Reports Pao Pereira Reduces BPH

    Benign prostatic hyperplasia (BPH) is one of the most common diseases in the urinary system of elderly men. Pao extract is an herbal preparation of the bark of the Amazon rainforest tree Pao Pereira (Geissospermum vellosii), which was reported to inhibit prostate cancer cell proliferation. Herein we investigated the therapeutic potential of Pao extract against BPH development in a testosterone-induced BPH rat model. The administration of testosterone induced the prostate enlargement, compared with the sham operated group with vehicle treatment. The BPH/Pao group showed reduced prostate weight comparable with BPH/finasteride group. Notably, Pao treatment did not significantly reduce body weights and sperm number of rats, compared with the control group. Furthermore, Pao extract treatment reduced the proliferative index in prostate glands and testosterone-induced expression levels of AR, as well as androgen-associated proteins such as SRD5A1 and PSA. Moreover, Pao extract and its active component, flavopereirine, induced cytotoxicity on human prostate epithelial RWPE-1 cells in a dose- and time- dependent manner with G2/M arrest. Consistently, Pao extract and flavopereirine suppressed the expression levels of SRD5A1, AR and PSA, respectively. Together, these data demonstrated that Pao extract suppresses testosterone-induced BPH development through inhibiting AR activity and expression, and suggested that Pao extract may be a promising and relative safe agent for BPH Treatment.

    BPH Treatment & Pao Pereira Data

    BPH Treatment Pao Pereria

    The figure above shows the effects of Pao extract on rat prostate. (a) Schematic presentation of experimental procedure. Sham group as control group: After sham operation, rats were treated with i.p. injection of corn oil and oral saline; BPH/Veh group: After castration, rats were i.p. injection of 5 mg/kg testosterone propionate (TP) daily and were intragastric administrated with saline; BPH/FN (Finasteride) and BPH/Pao groups: After castration, rats were i.p. injection of 5 mg/kg TP and intragastic administration of finasteride (10 mg/kg) or Pao extract (20 mg/kg) daily for 28 days, respectively. (b) The representative photos of the dissected prostate glands from four groups. (c) The weight of whole prostate without urethra. (d) The changes in the rat prostate index of four groups. (e) Effect of Pao extract on body weight. n = 5; **p < 0.01; ***p < 0.001.

    BPH Treatment Pao Pereria Figure 2

    The figure above shows the histopathological analysis of the prostate tissues in the testosterone-induced BPH rats after being treated with Pao extract. (a) H&E staining of the sham control, BPH/Veh, BPH/FN and BPH/Pao groups. The sections were photographed by microscope. The scale bars in photos above are 50 μm and in photos below are 20 μm. (b) Quantification of the thickness of epithelial layers; (c) quantification of the fold changes of the lumen areas among four groups. ***p < 0.001.

    Download Pao Pereira Extract Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by inhibiting 5α-Reductase

    Click here for more information about Pao pereira and prostate cancer

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  • Publication on the anti-cancer and anti-inflammatory activities of Pao pereira

    November 2013 – “Pao pereira Extract Suppresses Castration- Resistant Prostate Cancer Cell Growth, Survival and Invasion Through Inhibition of NFkB Signaling”

    by Cunjie Chang, BS, Wei Zhao, MS, Bingxian Xie, BS, Yongming Deng, BS, Tao Han, BM, Yangyan Cui, BS, Yundong Dai, BS, Zhen Zhang, BS, Jimin Gao, MD, PhD, Hongqian Guo, MD, PhD, and Jun Yan, PhD.
    Integr Cancer Ther. 2014 May;13(3):249-58. Doi: 10.1177/1534735413510557. Epub 2013 Nov 27

    Nanjing_UniversityDr. Jun Yan from Dr. Aaron Katz’s laboratory at Columbia University Medical Center is continuing research (University of Nanjing, China) on the anti-cancer and anti-inflammatory activities of Pao Pereira (extract provided by Natural Source International, Ltd.).

    Dr. Jun Yan uses up to date techniques to determine how the Pao pereira extract exerts its effects, what molecules it influences in the cell and what responses are triggered. The publication shows that this Pao pereira extract is effective against prostate cancer cells that no longer respond to agents that interfere with hormone action.

    Such drugs are specifically designed to limit the effects of testosterone, the male hormone that stimulates the growth of prostate cancer cells. Over time, prostate tumors become resistant to these anti-hormones indicting that the cancer has become more aggressive. The study shows that these hormone independent prostate cancer cells are susceptible to the growth inhibition of Pao pereira as are prostate cancers that still respond to testosterone. The study also revealed that Pao pereira acts on a signaling complex called NFkB—a control center regulating cell survival, proliferation, and invasion. The results suggest that Pao pereira will be useful for men with advanced hormone-independent prostate cancer.

    Abstractrauwolfia and ovarian cancer

    Pao extract, derived from bark of Amazonian tree Pao Pereira, is commonly used in South American medicine. A recent study showed that Pao extract repressed androgen-dependent LNCaP prostate cancer cell growth. We hypothesize that Pao extract asserts its anticancer effects on metastatic castration-resistant prostate cancer (CRPC) cells. Pao extract suppressed CRPC PC3 cell growth in a dose- and time-dependent manner, through induction of apoptosis and cell cycle arrest. Pao extract treatment induced cell cycle inhibitors, p21 and p27, and repressed PCNA, Cyclin A and Cyclin D1. Furthermore, Pao extract also induced the upregulation of pro-apoptotic Bax, reduction of anti-apoptotic Bcl-2, Bcl-xL , and XIAP expression, which were associated with the cleavage of PARP protein. Moreover, Pao extract treatment blocked PC3 cell migration and invasion. Mechanistically, Pao extract suppressed phosphorylation levels of AKT and NFκB/p65, NFκB DNA binding activity, and luciferase reporter activity. Pao inhibited TNFα-induced relocation of NFκB/p65 to the nucleus, NFκB/p65 transcription activity, and MMP9 activity as shown by zymography. Consistently, NFκB/p65 downstream targets involved in proliferation (Cyclin D1), survival (Bcl-2, Bcl-xL , and XIAP), and metastasis (VEGFa, MMP9, and GROα/CXCL1) were also downregulated by Pao extract. Finally, forced expression of NFκB/p65 reversed the growth inhibitory effect of Pao extract. Overall, Pao extract induced cell growth arrest, apoptosis, partially through inhibiting NFκB activation in prostate cancer cells. These data suggest that Pao extract may be beneficial for protection against CRPC.

    Pao pereira Extract Suppresses Castration- Resistant Prostate Cancer Cell Growth, Survival and Invasion Through Inhibition of NFkB Signaling”
  • Clinical Trial on the synergistic effects of Rauwolfia vomitoria and Pao pereira on elevated PSA

    April-May 2010 – “Two Herbal Extracts for Protecting Prostate Cell DNA – IMCJ April 2010”

    by Melissa Burchill, RN, CDN – IMCJ (Integrative Medicine: A Clinician’s Journal)

    A clinical trial began in 2006 and enrolled some 42 patients with elevated prostate specific antigen (PSA) readings (averaging 8 to 10 on the PSA scale) and a negative biopsy a group of men that in the industrialized world numbers in the millions.

    One of the primary goals of the clinical trial was to determine if the plant extracts were safe. The research team did a dose escalation trial. The trial started at two capsules but has gone much higher, and so far all doses tested have been without side effects.

    “We now know that this combination of Beljanski’s extracts can significantly lower PSAs in a 12-month period. Also we have had very few patients convert to prostate cancer and have found a number of patients who have had a dramatic improvement in their urinary symptoms. Men are clearly having less frequency, better streams and better flow rates. They are not getting up at night as often.

    “The bottom line is that it appears our early results are reason to be very encouraged by Beljanski’s extracts’ ability to lower PSA and help older men urinate better, too.”

    So how important are Beljanski’s findings to men’s health? “There are a lot of men undergoing PSA screening,” Dr. Katz said. “The PSA supposedly stands for “prostate specific antigen” but I say it is more accurately “patient stimulated anxiety.” When a man’s PSA is elevated, there could be many reasons for this, having nothing to do with cancer. But what we know now is that these cells that are growing can develop into cancer, and we would like to stop them from doing so. Also if the cells keep growing even in benign fashion, they will grow around the urethra and push in on it and provoke urinary symptoms in men. That’s where we want to lower the growth and division of prostate cells and that’s what we think we have shown with the extracts.

    Source: “The Columbia Connection” by L.Stephen Coles, MD., Ph.D. The Doctors’ prescription for healthy living

    Abstract

    Two Herbal extract prostateDuring his 50 years of research, biochemist and molecular biologist Mirko Beljanski, PhD, discovered 2 plant extracts that appeared to inhibit the growth of cancer cells without causing any harmful side effects. The research on these products and the preliminary indications from an ongoing clinical trial are the subject of this article. In summary, Dr Beljanski made great contributions to our understanding of basic life processes and cancer. He determined that, quite apart from the occurrence of genetic mutations of DNA, carcinogens can bind to and damage the DNA double helix, thus creating a destabilized and dysfunctional structure. Dr Beljanski associated this destabilization of the DNA with excess replication, aberrant gene expression, and increased cell multiplication, which are processes that may ultimately lead to cancer. To determine which substances cause DNA destabilization and thus can be considered carcinogenic, Dr Beljanski developed what he called the Oncotest as a way to determine the effect of a compound on the structure of DNA; compounds that enhanced either UV absorption or the level of in vitro DNA synthesis were considered to have carcinogenic properties. Through use of the Oncotest, Dr Beljanski also discovered 2 natural molecules from the tropical plants Pao pereira and Rauwolfia vomitoria that specifically recognized and bound to the damaged double helix, thus preventing the process of cell division. In vitro, these 2 natural extracts have been shown to inhibit the proliferation of a wide variety of cancer cells without affecting healthy cells. Experiments with animals confirmed these results, and preliminary work with humans has provided similar indications. Clinical studies using a combination of the pao and rauwolfia extracts have yielded encouraging preliminary results by reducing prostate-specific antigen levels in men and improving symptoms of benign prostatic hyperplasia.

    Two Herbal Extracts for Protecting Prostate Cell DNA – IMCJ April 2010
  • Publication on Pao Pereira Extract Against Prostate Cancer

    Spring 2009 – “β-Carboline Alkaloid-Enriched Extract from the Amazonian Rain Forest Tree Pao Pereira Suppresses Prostate Cancer Cells”

    by Debra L. Bemis, PhD, Jillian L. Capodice, LAc, MS, Manisha Desai, PhD, Aaron E. Katz, MD, Ralph Buttyan, PhD – Journal of the Society for Integrative Oncology, Vol 7, No2

    Columbia UniversityBark extracts from the Amazonian rain forest tree Geissospermum vellosii (pao pereira), enriched in B-carboline alkaloids have significant anticancer activities in certain preclinical models. Because of the predominance of prostate cancer as a cause of cancer-related morbidity and mortality for men of Western countries, the research team at Columbia University preclinically tested the in vitro and in vivo effects of a pao pereira extract against a prototypical human prostate cancer cell line, LNCaP. When added to cultured LNCaP cells, pao pereira extract significantly suppressed cell growth in a dose-dependent fashion and induced apoptosis. Immunodeficient mice heterotopically xenografted with LNCaP cells were gavaged daily with pao pereira extract or vehicle control over 6 weeks. Tumor growth was suppressed by up to 80% in some groups compared with tumors in vehicle-treated mice

    Prostate cancer is the most frequently diagnosed malignancy in males and a leading cause of cancer deaths in men.6 Given the relatively high frequency with which prostate cancer occurs, prevention offers the most likely means to reduce the health risk to men posed by the disease. If pao pereira bark extract has tumor-suppressing activity for prostate cancer without overt toxicity, one can consider the possibility that it might be used as a preventive agent as a dietary supplement.

    Abstract

    b carboline prostateBark extracts from the Amazonian rain forest tree Geissospermum vellosii (pao pereira), enriched in β-carboline alkaloids have significant anticancer activities in certain preclinical models. Because of the predominance of prostate cancer as a cause of cancer-related morbidity and mortality for men of Western countries, we preclinically tested the in vitro and in vivo effects of a pao pereira extract against a prototypical human prostate cancer cell line, LNCaP. When added to cultured LNCaP cells, pao pereira extract significantly suppressed cell growth in a dose-dependent fashion and induced apoptosis. Immunodeficient mice heterotopically xenografted with LNCaP cells were gavaged daily with pao pereira extract or vehicle control over 6 weeks. Tumor growth was suppressed by up to 80% in some groups compared with tumors in vehicle-treated mice. However, we observed a striking U-shaped dose-response curve in which the highest dose tested (50 mg/kg/d) was much less effective in inducing tumor cell apoptosis and in reducing tumor cell proliferation and xenograft growth compared with lower doses (10 or 20 mg/kg/d). Although this study supports the idea that a pao pereira bark extract has activity against human prostate cancer, our in vivo results suggest that its potential effectiveness in prostate cancer treatment may be limited to a narrow dose range.

    B-Carboline Alkaloid-Enriched Extract from the Amazonian Rain Forest Tree Pao Pereira Suppresses Prostate Cancer Cells
  • Publication on Rauwolfia Vomitoria extract against Prostate cancer

    July 2006 – “Anti-prostate cancer activity of B-carboline alkaloid enriched extract from Rauwolfia vomitoria”

    by D.L. Bemis, J.L. Capodice, P. Gorroochurn, A.E. Katz and R. Buttyan – International Journal of Oncology 29: 1065-1073

    Columbia UniversityThe tropical shrub, Rauwolfia vomitoria, is a medicinal plant used traditionally to treat a variety of ailments. A bioactive ß-carboline alkaloid, alstonine, present in this extract was previously shown to have anti-cancer activity against cancer cell lines.

    This study considers the potential anti-prostate cancer activity of this extract in vitro and in vivo. Rauwolfia vomitoria extract standardized for ß-carboline alkaloids was tested for ability to influence the growth and survival of the human LNCaP prostate cancer cell line. A WST-1 assay was used to measure cell growth, and cell cycle analyses were conducted with flow cytometry. Western blot detection of PARP cleavage and accumulation of cells containing subgenomic DNA indicated induction of apoptosis. Pathway specific microarray analyses were utilized to identify the effect of Rauwolfia extract on the expression of 225 genes. Mice xenografted with LNCaP cells were treated with the extract or placebo control, and tumor growth was measured for 5 weeks.

    The effects of the extract on xenografted tumor cell proliferation and apoptosis were measured by in situ BrdU incorporation and TUNEL staining. Rauwolfia extract decreased in vitro cell growth in a dose-dependent manner (p<0.001) and induced the accumulation of G1 phase cells. PARP cleavage demonstrated that apoptosis was induced only at the highest concentration tested (500 μg/ml) which was confirmed by detection of cells containing subgenomic DNA.

    The expression of genes associated with DNA damage signaling pathway was up-regulated by Rauwolfia treatment, including that of GADD153 and MDG. The expression of a few cell cycle genes (p21, cyclin D1 and E2F1) was also modulated. These alterations were confirmed by RT-PCR. Tumor volumes were decreased by 60%, 70% and 58% in the groups fed the 75, 37.5 or 7.5 mg/kg Rauwolfia, respectively (Kruskal-Wallis test, p<0.001). The Rauwolfia vomitoria extract significantly suppressed the growth and cell cycle progression of LNCaP cells, in vitro and in vivo.

    The data presented herein suggest that this plant extract has anti-prostate cancer activity in both in vitro and in vivo model systems which, based upon our analyses of gene expression patterns of treated prostate cancer cells, may be modulated by its effects on DNA damage and cell cycle control signaling pathways.

    Abstract

    anti prostate cancer activityThe tropical shrub, Rauwolfia vomitoria, is a medicinal plant used traditionally to treat a variety of ailments. A bioactive ß-carboline alkaloid, alstonine, present in this extract was previously shown to have anti-cancer activity against cancer cell lines. This study considers the potential anti-prostate cancer activity of this extract in vitro and in vivo. Rauwolfia vomitoria extract standardized for ß-carboline alkaloids was tested for ability to influence the growth and survival of the human LNCaP prostate cancer cell line. A WST-1 assay was used to measure cell growth, and cell cycle analyses were conducted with flow cytometry. Western blot detection of PARP cleavage and accumulation of cells containing sub-genomic DNA indicated induction of apoptosis. Pathway specific microarray analyses were utilized to identify the effect of Rauwolfia extract on the expression of 225 genes. Mice xenografted with LNCaP cells were treated with the extract or placebo control, and tumor growth was measured for 5 weeks. The effects of the extract on xenografted tumor cell proliferation and apoptosis were measured by in situ BrdU incorporation and TUNEL staining. Rauwolfia extract decreased in vitro cell growth in a dose-dependent manner (p<0.001) and induced the accumulation of G1 phase cells. PARP cleavage demonstrated that apoptosis was induced only at the highest concentration tested (500 μg/ml) which was confirmed by detection of cells containing sub-genomic DNA. The expression of genes associated with DNA damage signaling pathway was up-regulated by Rauwolfia treatment, including that of GADD153 and MDG. The expression of a few cell cycle genes (p21, cyclin D1 and E2F1) was also modulated. These alterations were confirmed by RT-PCR. Tumor volumes were decreased by 60%, 70% and 58% in the groups fed the 75, 37.5 or 7.5 mg/kg Rauwolfia, respectively (Kruskal-Wallis test, p<0.001). The Rauwolfia vomitoria extract significantly suppressed the growth and cell cycle progression of LNCaP cells, in vitro and in vivo.

    Anti-prostate cancer activity of B-carboline alkaloid enriched extract from Rauwolfia vomitoria