Inhibition of breast cancer progression by a medicinal herb Ocimum sanctum
Ocimum sanctum (OS) also known as holy basil or tulsi, belonging to mint family (Labiateae) has been one of the most popular herbs used in European and Asian countries for the treatment of various ailments since ancient times. We reported earlier that aqueous extracts collected from the leaves of this herb inhibited chemotaxis of breast cancer cell lines MDA-MB-435, MDA-MB-231 and endothelial cell line HUVEC towards specific chemo attractants, capillary tube formation in 3 dimensional cultures of HUVEC on Matrigel, TPA induced increase of COX-2 in MDA-MB-231 cells, and MDA-MB-231 cells induced angiogenesis in Matrigel plug assay in nude mice. To explore if OS extracts have an inhibitory effect on breast cancer, we used two human breast cancer cell lines for tumorigenic studies; namely MDA-MB-435 and MCF10A DCIS.com (DCIS.com) cells. MDA-MB-435 cells form undifferentiated adenocarcinomas in nude mice. Injection of DCIS.com cells into nude mice results in lesions that are predominantly DCIS subtype. In 3 weeks, the lesions show a DCIS like pathology consisting of ducts surrounded by complete basement membrane and extensive angiogenesis in the stroma.
The ducts develop into a complete comedo phenotype by 6 weeks. When OS extracts were fed to nude mice injected with MDA-MB-435 or DCIS.com cells, there was a significant reduction in the rate of tumor growth in the treated mice. The tumors in OS fed mice grew at similar rates as the water fed controls initially, though their overall size was smaller than the controls. After reaching a tumor volume of approximately 150mm3 in DCIS.com or 200 mm3 in MDA-MB-435 the growth rate started to slow down. The inhibition in tumor growth was due to reduced cell proliferation and angiogenesis as indicated by immunohistochemical analysis utilizing anti CD34 (neo angiogenesis) and anti proliferating cell nuclear antigen (PCNA) antibodies. Furthermore, there was also a reduced expression of COX-2, MMP-9 and redistribution of VEGF from stromal epithelial compartments to epithelial compartment in the OS treated xenografts. A comparative analysis of the temporal development between normal and OS treated DCIS.com xenografts indicates a delay towards progression to DCIS-like phenotype by oral administration of OS. Based on our data we conclude that OS extract inhibit tumor growth and progression by affecting cell proliferation and angiogenesis and it could be developed into a breast cancer preventive and therapeutic agent.