Milestone in Cancer Stem Cell Research

Pao Pereira Fights Cancer Stem Cells!

New research just published in Integrative Cancer Therapies shows that the Pao pereira plant extract inhibits pancreatic cancer stem cells. This dramatic result means that the extract will be useful for preventing cancer recurrence.

Everyone knows that cancer treatments are not cancer cures. Chemotherapy treatments kill cancer cells and shrink tumors, but the cancer often comes back. Cancer stem cells (CSCs) are the culprit because they are resistant to anti-cancer drugs, they can metastasize and form new tumors. CSCs make up a small fraction of the cells in a tumor that survive after the majority of primary cancer cells are killed by anti-cancer drugs. The CSCs persist, spread and restart tumor growth.

CSCs are also referred to as cancer stem-like cells because they share the capacity for self-proliferation with normal stem cells that are involved in the renewal and repair of tissues, but unlike normal stem cells, CSCs are cancerous and drug resistant.

In vitro experiments show Pao pereira reducing the number of pancreatic CSCs (see figure below).

As the amount of Pao pereira is increased, the number of pancreatic cancer stem cells (spheroids) decrease dramatically. In additional cell-based studies, the Pao pereira extract also specifically reduced the pancreatic cancer stem cell population.

In vivo experiments showed that Pao pereira inhibited the capacity of pancreatic CSCs to form tumors – the defining characteristic of CSCs – and significantly reduce the volume of tumors that did form (see figure below).

At day 6 (Figure A), tumor formation rate in the control group reached 80%, while in Pao-treated group it was only 10%. At day 20, when the treatment stopped, all mice in control group were bearing tumors on both flanks (100% tumor formation), while the Pao-treated group only had 30% tumor formation. Growth of the formed tumors was also inhibited by Pao pereira treatment compared with the control group (Figure B). A long-term inhibitory effect in tumor growth was observed after treatment had stopped. Pao pereira works by lowering the signals that trigger the pancreatic cancer stem-like cell properties that lead to cancer recurrence.

The researchers at Kansas University Medical Center concluded that Pao pereira holds great promise as a novel treatment for targeting pancreatic CSCs, an essential component of treatments that will lead to real cancer cures.

Publication:

Extract of the Medicinal Plant Pao Pereira Inhibits Pancreatic Cancer Stem-Like Cell In Vitro and In Vivo.

Dong, P. Chen and Q Chen. Integrative Cancer Therapies. July 2018.

All Green Teas are Not Equal in Anti-Cancer Effect

All Green Teas are Not Equal in Anti-Cancer Effect:  Research shows that a special green tea blend is more effective against breast cancer.

 

Results:

The results of a new study comparing the anti-cancer effects of several well-known teas has shown that a newly developed blend of green teas was superior at inhibiting the growth of two breast cancer cell lines, including one highly metastatic cell line. This blend combines four different green teas: Ceylon Green, Bi Lou Chun, Organic Gunpowder and Dragonwell.

Blend of teas selected by Mirko Beljanski

The anti-cancer potential of each of these teas was originally identified by Prof. M. Beljanski of the Pasteur Institute using the Oncotest, an assay he developed for detecting carcinogenic and anti-carcinogenic compounds. The new study confirms the activity of a combination of the four green teas against breast cancer cells.

Green teas have long been associated with anti-oxidant and anti-cancer benefits, but the new research shows that the activity of this specific combination stands out. When tested against other teas including Bigelow®, Kusmi®, and Lipton®, the four green tea blend had the most potent anti-cancer effect on the cultured breast cancer cells. Data in the figure below show the viability of the breast cancer cell lines after exposure to extracts of each of the teas tested (400 micrograms/ml). The green tea blend (OnkoTeaTM) was the best at reducing the number of breast cancer cells.

Onkotea and breast cancer

This research was conducted at a prominent medical center that has conducted many successful projects on behalf of The Beljanski Foundation.  Further research is planned to explore the effects of the green tea blend on other types of cancer.

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.

Abstract

Pao pereira Extract Suppresses Castration Resistant Prostate Cancer Cell Growth

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.

Download Pao pereira Extract Suppresses Castration- Resistant Prostate Cancer Cell Growth, Survival and Invasion Through Inhibition of NFkB Signaling

Clinical trial with Beljanski’s RNA Fragments Beljanski

October 2010 – 'Dose Escalation Study of an Antithrombacytopenic Agent in Patients with Chemotherapy Induced Thrombocytopenia'

by Robert D Levin, MaryAnn Daehler, James F Grutsch, John L Hall, Digant Gupta, Christopher G Lis. Levin
Online magazine Bio Med Central BMC Cancer 10:565 – 2010.

Cancer Treatment Center of America

Cancer Treatment Centers Of America logo. (PRNewsFoto/CANCER TREATMENT CENTERS OF AMERICA)

Low platelet counts, a condition called Thrombocytopenia, is a side effect of chemo drugs that damage the bone marrow stem cells that normally produce platelets. The Phase I trial showed that Beljanski's RNA fragments could prevent thrombocytopenia by inducing the production of new platelets. Patients taking the RNA fragments had their platelet levels return to normal and chemotherapy treatments were completed without dose reductions, platelet transfusions, or suspensions. The RNA fragments protected platelet levels in patients with many different types of cancer who were taking many different anti-cancer drugs. Moreover, patients did not suffer any negative side effects as a result of taking the RNA fragments. The results suggest further studies aimed at establishing the RNA fragments as a standard component in all chemotherapies that cause significant platelet loss.

CTCA - RNA FragmentsThe Prestigious Cancer Treatment Centers of America® (CTCA) have completed a clinical trial on the Beljanski's formula of RNA fragments, which was conducted among cancer patients undergoing different chemotherapies. Thanks to the RNA fragments prepared according to Dr. Beljanski's proprietary process, the cancer patients all recovered a stronger immune system and managed to go through the end of their chemotherapy treatment without getting thrombocytopenia – a frequent and dangerous side effect of the chemotherapy drugs.

Abstract

Background: Preclinical studies demonstrated that small chain RNA fragments accelerate the recovery of platelets numbers in animals exposed to high doses of chemotherapeutic drugs. There is anecdotal data supporting the same application in humans. The Phase I clinical trial described here was designed to investigate the relationship between the administration of small chain RNA fragments and the recovery in platelets following Chemotherapy Induced Thrombocytopenia (CIT).

Methods: Cancer patients with solid tumors that experienced post chemotherapy thrombocytopenia with a nadir of < = 80,000 platelets/ml were eligible for this clinical trial. There were no exclusions based on ECOG status, tumor type, tumor burden or chemotherapeutic agents. Patients received a unique preparation of RNA derived from either E. coli or yeast. Ten patients per group received 20, 40, or 60 mg as a starting dose. Subjects selfadministered RNA fragments sublingually on an every other day schedule while undergoing chemotherapy. The dose was escalated in 20 mg increments to a maximum dose of 80 mg if the nadir was < 80,000 platelets/ml at the start of the next cycle. Subjects were treated for three cycles of chemotherapy with the maximum effective dose of RNA fragments. Subjects continued on planned chemotherapy as indicated by tumor burden without RNA fragment support after the third cycle. Subjects kept a diary indicating RNA fragment and magnesium administration, and any experienced side effects.

Results: Patients receiving E. coli RNA fragments demonstrated a more rapid recovery in platelet count and higher nadir platelet count. None of the patients receiving the E. coli RNA fragments required a chemotherapy dose reduction due to thrombocytopenia. The optimal dose for minimizing CIT was 80 mg. Conversely, subjects receiving yeast RNA fragments with dose escalation to 80 mg required a chemotherapy dose reduction per American Society of Clinical Oncology guidelines for grade 3 and 4 thrombocytopenia.

Conclusions: Patients receiving myelosuppressive chemotherapy experienced an improvement in the platelet nadir and shorter recovery time when receiving concurrent E coli RNA fragments, when compared to patients who received yeast RNA fragments. These data indicate that 60 and 80 mg doses of E. coli RNA accelerated platelet recovery. Further clinical investigations are planned to quantify the clinical benefits of the E. coli RNA at the 80 mg dose in patients with chemotherapy induced thrombocytopenia.

Trial Registration: Clinical Trials.gov Identifier: NCT01163110

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Publication on Rauwolfia Vomitoria Extract against Pancreatic Cancer

March 2014 – 'Antitumor Activities of Rauwolfia vomitoria Extract and Potentiation of Gemcitabine Effects Against Pancreatic Cancer'

by Jun Yu, PhD and Qi Chen, PhD
Integrative Cancer Therapy. 2014 Apr 24;13(3):217-225.

Kansas universityThe fourth publication from the scientific collaboration between the Beljanski Foundation and Kansas University Medical Center has been released. It shows, in vitro and in vivo, the effectiveness of Rauwolfia vomitoria (the extract prepared according to Dr. Mirko Beljanski's proprietary process) on pancreatic cancer cells. This publication also confirms – if confirmation were needed – the non-toxicity of Rauwolfia ('Rau'), on healthy cells, its selective effect against cancer cells, and its excellent synergistic action with Gemcitabine chemotherapy. This study, conducted with extracts provided by Natural Source International, Ltd. is now available on The Beljanski Foundation website.

For the purpose of this study, pancreatic cancer cells were inoculated into four groups of mice (control group treated with saline solution, mice treated with Gemcitabine alone, mice treated with Rauwolfia alone, and mice with combination treatment of Gemcitabine and Rauwolfia). As the tumors did not respond to Gemcitabine, Rauwolfia at either 20 mg/kg or 50 mg/kg provided observable inhibition in tumor growth. The combination of Gemcitabine + Rauwolfia at both doses also inhibited tumor progression. Notably, there were 2 mice in the Gemcitabine + Rauwolfia 50 mg/kg group that had complete tumor regression, an effect that was not observed in any other treatment group.

Necropsy confirmed the imaging results at the end of the treatment. Gemcitabine at the dose used did not provide any reduction in tumor weight, when Rauwolfia alone decreased tumor weight by 53% at the daily dose of 20 mg/kg, and 46% at the daily dose of 50 mg/kg, compared with saline-treated control. By combining Rauwolfia with Gemcitabine, the decrease in tumor weight was 56% at both Rauwolfia doses. The improvement in tumor inhibition provided by the combination was significant compared with that of Gemcitabine alone.

On assessing tumor metastasis, 12% of mice in the control group (saline-treated) and in the Rauwolfia 20 mg/kg group did not form metastasis, whereas all mice in Gemcitabine group formed metastasis. The percentage of metastasis free mice increased to 40% with both Rau 50 mg/kg treatment and Gemcitabine + Rauwolfia treatment, suggesting that Rauwolfia provided benefit in reducing metastatic potential while Gemcitabine did not.

None of the mice demonstrated observable toxicity associated with the treatments. At the end of the experiments, major organs (kidney, liver, and spleen) were subjected to hematoxylin and eosin staining and histopathological analysis. No tissue damage was detected in the treatment groups, and there were no significant differences between the control group and the treated group. This data demonstrated that Rauwolfia at the dose used, either alone or combined with Gemcitabine, was effective and, at the same time, low in toxicity.
This would open an avenue to reduce toxicity associated with chemotherapy.

Abstract

Pancreatic cancer is one of the most lethal malignancies with very limited treatment option. In the effort of enhancing the effect of the conventional chemotherapeutic drug gemcitabine against pancreatic cancer, we investigated in vitro and in vivo the anticancer effect of a β-carboline-enriched extract from the plant Rauwolfia vomitoria (Rau), either alone or in combination with gemcitabine, in preclinical pancreatic cancer models. Rau induced apoptosis in pancreatic cancer cells in a concentration-dependent manner, and completely inhibited colony formation of PANC-1 cells in soft agar.
The combination of Rau and gemcitabine had synergistic effect in inhibiting cell growth with dose reduction effect for gemcitabine. In an orthotopic pancreatic cancer mouse model, PANC-1 tumor growth was significantly suppressed by Rau treatment. Metastasis was inhibited by Rau. Adding Rau to gemcitabine treatment reduced tumor burden and metastatic potential in the gemcitabine non-responsive tumor. These data suggest that Rau possesses anti–pancreatic cancer activity and could improve effect of gemcitabine.

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Publication on Pao pereira Extract against Pancreatic Cancer

March 2013 – 'Inhibition of Pancreatic Cancer and Potentiation of Gemcitabine Effects by the Extract of Pao Pereira'

by JUN YU, JEANNE DRISKO and QI CHEN
Oncology Reports' Journal (doi: 10.3892/or.2013.2461)

Kansas universityThe scientific team at the University of Kansas Medical Center has just published a new article entitled, 'Inhibition of Pancreatic Cancer and Potentiation of Gemcitabine Effects by the Extract of Pao Pereira' in the 'Oncology Reports' Journal (doi: 10.3892/or.2013.2461).

This scientific paper describes the results of in vitro and in vivo studies demonstrating the anti-cancer effect of the Pao pereira extract, used alone and in combination with gemcitabine (chemotherapy used in most cancer treatments), in multiple cancer cell lines including those of the pancreas resistant to anti-mitotic drugs.

Pre-clinical studies conducted with mice, both in vitro an in vivo, confirm that adding Pao Pereira to the treatment regiment reduced the concentration of Gemcitabine to produce an equitoxic effect on pancreatic cancer cells. The Pao's anti-cancer effect was seen in vivo and in vitro working alone and in conjunction with other chemotherapy treatments. Over the course of the study, the Pao pereira was seen to suppress tumor growth significantly, by up to 72%.

This confirms another study, published just a few years ago, out of Columbia University demonstrating that the two plant extracts, Pao Pereira and Rauwolfia Vomitoria, contain Beta-Carbolines with effective anti-cancer properties which inhibit cancer cell growth, even in those cells resistant to drugs used in chemotherapy. This study, specific to anti-prostate cancer activity, also substantiated that all healthy cells were not negatively affected, thus demonstrating the safety of the plant extracts prepared by the Beljanski method.

With such promising initial results, the research will continue on Pao Pereira to assess its effectiveness on other types of cancerous cells!

Abstract

Kansas - Pao - PancreasLack of effective therapy is a major problem in the treatment of pancreatic cancer. In the present study, we investigated a natural product, the extract of Pao Pereira (Pao), for its anti-pancreatic cancer effect in vitro and in vivo, either alone or in combination with the first-line chemotherapeutic drug gemcitabine (Gem). Pao induced dose-dependent apoptosis to all five tested pancreatic cancer cell lines. The combination of Pao and Gem had a synergistic effect in the inhibition of cell growth, with combination indices (CIs)

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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.

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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.

Download B-Carboline Alkaloid-Enriched Extract from the Amazonian Rain Forest Tree Pao Pereira Suppresses Prostate Cancer Cells

Publication on Rauwolfia Vomitoria Extract Against Ovarian Cancer

November 2013 – 'Antitumor Activities of Rauwolfia Vomitoria Extract and Potentiation of Carboplatin Effects Against Ovarian Cancer'

Yu J, Ma Y, Drisko J, Chen Q.
Curr Ther Res Clin Exp. 2013 Dec;75:8-14. doi: 10.1016/j.curtheres.2013.04.001.

Kansas universityDrs. Qi Chen and Jeanne Drisko at Kansas University Medical Center (KUMC) have been interested in ovarian as well as pancreatic cancer and have explored the potential of the Pao Pereira and Rauwolfia vomitoria extracts as alternative therapeutic agents for these cancers.

Like pancreatic cancer, ovarian cancer is frequently diagnosed late; it also develops drug resistance and is similarly difficult to treat. Following the same line of experiments used for testing the Pao Pereira extract against pancreatic cancer the researchers at KUMC studied the anti-ovarian cancer effects of the Rauwolfia vomitoria extract.

They found that Rauwolfia vomitoria was effective against ovarian cancer cells both alone and in combination with carboplatin. The combination decreased tumor size in animal experiments by 87 to 90%.

These dramatic results indicate that in the presence of Rauwolfia, drug resistance of the tumor cells is overcome and the activity of carboplatin is restored. The authors conclude that, 'Rauwolfia vomitoria has potent anti-tumor activity and in combination significantly enhances the effect of carboplatin against ovarian cancer.'

Abstract

rauwolfia and ovarian cancerTumor resistance to platinum-based drugs has been an obstacle to the treatment of ovarian cancer. Extract of the plant Rauwolfia vomitoria has long been used by cancer patients. However, there have not been systematic studies of its anticancer activity. Objective: In an effort to enhance the effectiveness of platinum-based drugs, we investigated the anticancer effect of a Rauwolfia vomitoria extract (Rau), both alone and in combination with carboplatin (Cp). Methods: In vitro cytotoxicity and colony formation were evaluated in several ovarian cancer cell lines. In vivo effects were evaluated in an intraperitoneal ovarian cancer mouse model. The combination of Rau and Cp was assessed using Chou-Talalay's constant ratio design and median effect analysis based on the isobologram principle to determine the combination index values. Results: Rau decreased cell growth in all 3 tested ovarian cancer cell lines dose dependently and completely inhibited formation of colonies in soft agar. Apoptosis was induced in a time- and dosedependent manner and was the predominant form of Rau-induced cell death. Synergy of Rau with Cp was detected, with combination index values o1 and dose reduction index values for Cp ranging from 1.7- to 7-fold. Tumor growth in mice was significantly suppressed by 36% or 66% with Rau treatment alone at a low (20 mg/kg) or a high dose (50 mg/kg), respectively, an effect comparable to that of Cp alone. The volume of ascitic fluid and the number of nonblood cells in ascites were also significantly decreased. Combining Rau with Cp remarkably enhanced the effect of Cp and reduced tumor burden by 87% to 90% and ascites volume by 89% to 97%. Conclusions: Rau has potent antitumor activity and in combination significantly enhances the effect of Cp against ovarian cancer.

©2013. The Authors. Published by Elsevier Inc. All rights reserved.

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Publication on Pao Pereira Extract Against Ovarian Cancer

September 2013 – 'The Plant Extract of Pao Pereira Potentiates Carboplatin Effects Against Ovarian Cancer' published by Informa Healthcare USA, Inc.

Jun Yu, PhD, Qi Chen, PhD.  – ISSN 1388-0209 print/ISSN 1744-5116 –
Pharmaceutical Biology

Kansas universityRecent research conducted at the University of Kansas Medical Center shows that an herbal preparation of Pao pereira, provided by Natural Source International, Ltd. could be extremely helpful.  It concludes that 'In vivo, Pao pereira alone suppressed tumor growth by 79% and decreased volume of ascites by 55%. When Pao pereira was combined with carboplatin, tumor inhibition reached 97% and ascites was completely eradicated. Pao pereira possess potent antitumor activity and could enhance carboplatin effect, and therefore holds therapeutic potential in the treatment of ovarian cancer.'

This is a breakthrough study considering that The American Cancer Society estimates that in 2013, about 22,240 new cases of ovarian cancer will be diagnosed and 14,030 women will die of ovarian cancer in the United States. According to the data, the mortality rates for ovarian cancer have not improved in the forty years since the 'War on Cancer' was declared.

The herbal preparation of Pao pereira long been used by oncologic patients and Integrative Medicine practitioners in South America. This study investigates the anticancer effects of Pao pereira (Pao), either alone or in combination with chemotherapy drugs (carboplatin), in preclinical ovarian cancer models.

The results of the study offer a breakthrough for ovarian cancer research!

Pao pereira selectively inhibited ovarian cancer cell growth but induced apoptosis (programmed cell death) and also Pao pereira greatly enhanced chemo drug cytotoxicity.

In vivo, Pao pereira alone suppressed tumor growth by 79% and decreased volume of ascites by 55%. When Pao pereira was combined with Chimio therapy, tumor inhibition reached 97% and ascites was completely eradicated.
The researchers conclude that Pao Pereira has therapeutic potential in the treatment of ovarian cancer.

Abstract

Herbal preparation of Pao pereira [Geissospermum vellosii Allem (Apocynaceae)] has long been used by oncologic patients and Integrative Medicine practitioners in South America. However, its anticancer activities have not been systematically studied. Objective: To investigate the anticancer effects of b-carboline alkaloids-enriched extract from Pao pereira (Pao), either alone or in combination with carboplatin, in preclinical ovarian cancer models. Materials and methods: Cytotoxicity of Pao (0–800 mg/ml) against different ovarian cancer cell lines and an immortalized epithelial cell line was detected by flow cytometry, MTT assay and colony formation in soft agar. Combination of Pao and carboplatin, a primary chemotherapeutic drug for ovarian cancer, was evaluated using Chou-Talalay's methods. Mice bearing intraperitoneally spread ovarian cancer were treated with 20 or 50 mg/kg/day Pao by i.p. injection. Carboplatin at 15 mg/kg/week i.p. was compared and combined to Pao treatments. Results: Pao selectively inhibited ovarian cancer cell growth with IC50 values of 180–235 mg/ml, compared to 537 mg/ml in normal cells. Pao induced apoptosis dose- and time-dependently and completely inhibited colony formation of tumor cells in soft agar at 400 mg/ml. Pao greatly enhanced carboplatin cytotoxicity, with dose reduction (DRIs) for carboplatin at 1.2–10 fold. In vivo, Pao alone suppressed tumor growth by 79% and decreased volume of ascites by 55%. When Pao was combined with carboplatin, tumor inhibition reached 97% and ascites was completely eradicated. Discussion and conclusion: Pao possess potent antitumor activity and could enhance carboplatin effect, and therefore holds therapeutic potential in the treatment of ovarian cancer.

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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.

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