Inhibition of tumor angiogenesis by Brahma Rasayana (BR).
The current therapy for prostate cancer includes radical prostatectomy, radiation therapy and hormonal ablation. Chemotherapy also provides beneficial 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 that 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 BR treated animals in comparison to untreated controls. In the present study, we focused to examine the effect of BR on angiogenesis and regulation of molecular markers involved in angiogenesis using in-vivo and in-vitro models. 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 pro-angiogenic 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 BR in the reduction of tumor growth and metastatic spread.
Thangapazham
Rajesh L
RL
Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Sharma
Anuj
A
Gaddipati
Jaya P
JP
Singh
Anoop K
AK
Maheshwari
Radha K
RK
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005169:Factor VIII / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000975:Antioxidants; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; C403274:brahma rasayana; D005169:Factor VIII; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9