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Curr Ther Res Clin Exp. 2013 Dec; 75: 8–14.
doi: 10.1016/j.curtheres.2013.04.001
PMCID: PMC3898180
PMID: 24465036
Antitumor Activities of Rauwolfia vomitoria Extract and Potentiation of Carboplatin Effects Against Ovarian Cancer☆
Jun Yu, PhD,1,2 Yan Ma, PhD,1,2 Jeanne Drisko, MD,2 and Qi Chen, PhD1,2,⁎

With an estimated 22,280 new cases and 15,500 deaths in the United States in 2012, ovarian cancer causes more death than any other cancer of the female reproductive system.1 Due to the lack of significant symptoms in the early stages and the absence of effective biomarkers for early detection, ovarian cancer is usually diagnosed in patients at a late stage of the disease.2–4 As a result, these patients have a poor prognosis and severely impaired quality of life. Although current primary therapy can improve the 5-year survival rate, it has not increased the overall rate of cure.1,4 This is because >70% of patients experience a relapse and develop a resistance to platinum- and taxane-based treatments.4,5 Malignant ascites resistant to conventional chemotherapy affect 28% of ovarian cancer patients in their last period of life.6 Effective and novel treatment strategies for advanced ovarian cancer are urgently needed.

Background
Tumor 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 dose-dependent manner and was the predominant form of Rau-induced cell death. Synergy of Rau with Cp was detected, with combination index values <1 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.
Key words: carboplatin, ovarian cancer, plant extract, Rauwolfia vomitoria, synergy