Ovarian cancer: Rauwolfia Vomitoria and Pao Pereira

Why did we choose to focus on Ovarian Cancer ?

Ovarian and pancreatic cancers have several things in common.
First, both these cancers often do not cause any obvious symptoms so the victims do not know something serious is wrong. This means that both cancers are diagnosed relatively late which limits treatment options.
Second, the tumor cells in both ovarian and pancreatic cancers usually become resistant to the drugs chosen for treatment.

This means that the tumors may be reduced in the first stage of therapy, but when the cancer cells become resistant to the toxic effect of the drugs, they keep growing even in the presence of the drugs. As a result of these shared problems, the prognosis for patients with ovarian or pancreatic cancer is bleak so there is a compelling need for innovative treatments for ovarian and pancreatic cancer including an urgent need for agents that overcome the chemo-resistance characteristic of these tumors.

Following the successful research at Columbia University Medical Center on prostate cancer, The Beljanski Foundation decided to extend its research program to focus on ovarian and pancreatic cancers. Our interests matched those of Dr. Jeanne Drisko and Dr. Qi Chen in the Department of Pharmacology, Toxicology and Therapeutics at Kansas University Medical Center.
Dr. Chen used cell-based assays to show that the Pao pereira (formerly known as PB-100) and Rauwolfia vomitoria extracts (provided by Natural Source International, Ltd) inhibited the growth of multiple ovarian and pancreatic cancer cell lines, including cells that are resistant to chemo drugs. Dr. Chen went on to show that the Pao Pereira or the Rauwolfia vomitoria extracts combined with either Carboplatin (ovarian) or Gemcitabine (pancreatic) worked especially well even against drug resistant ovarian and pancreatic cancer cells. The extracts have anti-cancer activities of their own, but also appear to overcome drug resistance.

The results of the animal studies conducted at KUMC were impressive. The Pao pereira and Rauwolfia vomitoria extracts reduced ovarian and pancreatic tumor size by themselves, but also worked to enhance the activity of the chemo drugs. For example, in the case of ovarian cancer, “Pao pereira alone suppressed tumor growth by 79%….when Pao pereira was combined with Carboplatin, tumor inhibition reached 97%.” The results indicate that Pao pereira and Rauwolfia vomitoria hold therapeutic promise for pancreatic as well as ovarian cancer.

Cancer is a disease in which certain body cells don’t function right, divide very fast, and produce too much tissue that forms a tumor. Ovarian cancer is cancer in the ovaries, the female reproductive organs located in the pelvis. The ovaries produce female hormones and store eggs that, if fertilized by sperm, can develop into a baby. Women have two ovaries, one on each side of the uterus. Tumors found in the ovaries may be non‑cancerous tissue growths (cysts) or cancerous growths that may spread to other parts of the body.

About 1 in every 72 women in the United States will develop ovarian cancer. Most cases occur in women over the age of 50, but this disease can also affect younger women. Ovarian cancer causes more deaths than any other cancer of the female reproductive system. The sooner ovarian cancer is detected and treated, the better a woman’s chance for recovery. But ovarian cancer is hard to detect early. Many times, women with ovarian cancer have no symptoms or just mild symptoms until the disease is in an advanced stage. Scientists are studying ways to detect ovarian cancer before symptoms develop.
source: http://www.womenshealth.gov/publications/our-publications/fact-sheet/ovarian-cancer.cfm

Our Partner for those publications: Kansas University Medical Center

Kansas universityThe University of Kansas Medical Center is located in Kansas City, Kansas, and comprises the schools of medicine, nursing and allied health.

The University of Kansas Medical Center serves Kansas through excellence in education, research, patient care and community engagement.

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Our publications

  • 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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