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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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 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 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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