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).
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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.
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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.
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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.
- 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
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.
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
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.
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.
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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
Dr. 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.
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
During 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