Titre de la Publication: “Activités antitumorales de l’extrait de Rauwolfia vomitoria et potentialisation des effets de la gemcitabine contre le cancer du pancréas”

Publié par ” Integrative Cancer Therapy “

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

The 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.