The current therapy for prostate cancer includes radical prostatectomy, radiation therapy and hormonal ablation. Chemotherapy also provides beneficiary results for some patients with advanced prostate cancer but with several harmful side effects. Hence there is a need to identify and develop alternate therapies, which can reduce the disease progression with minimal or few side effects. Earlier studies from our laboratory have shown a Polyherbal mixture, Brahma rasayna (BR) rich in anti-oxidant principles has a potential to be an anti-tumor agent. BR treatment of MAT-LyLu cell inoculated Copenhagen rats resulted in a decrease of palpable tumor incidence, delay in tumor occurrence and lower mean tumor volumes. Also a significant reduction in tumor weight and lung metastasis was observed in rasayana treated animals in comparison to untreated controls. As we observed a reduction in tumor volume and metastasis, we focused our present study to examine the effect of BR on angiogenesis and regulation of molecular markers involved in angiogenesis. Analysis included estimation of micro vessel density by Factor VIII staining and expression of angiogenic regulators such as VEGF, MMP-9 and MMP-2 by Western blotting and zymograms, in tumor tissues from rasayana treated and untreated animals. We also conducted in vitro angiogenesis assays to study the effect of BR on cell migration, invasion and differentiation in human umbilical vein endothelial cells (HUVEC). BR treatment showed a significant reduction in Factor VIII expression compared to control indicating reduced angiogenesis. BR treated tumor specimens showed a decrease in the proangiogenic factors like VEGF, MMP-9 and MMP-2. Methanolic extract of BR was found to inhibit the proliferation, tube formation, cell migration and attachment of HUVEC on matrigel in a dose dependant manner. These findings suggest the possible mechanism(s) of action of Brahma rasayana in the reduction of tumor growth and metastatic spread.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]