Prospective validation in appropriately sized and controlled studies is therefo

STB HO inhibits VEGF mediated proliferation and phosphorylation of VEGFR2 and Akt in HUVECs As shown in Figure 6A, MTT assay revealed that STB HO did not show any cytotoxicity in HUVECs as a nor mal cell line. Also, to confirm antiangiogenic activity of STB KU-0063794 分子量 HO in HUVECs, proliferation assay was performed in VEFG treated HUVECs by MTT assay. As shown in Figure 6B, STB HO inhibited VEGF induced proliferation of HUVECs in a dose dependent manner at nontoxic con centrations in HUVECs. In addition, as shown in Figure 7, STB HO suppressed the phosphorylation of VEGFR 2 and Akt in HUVECs compared to untreated control. Discussion There are evidences that minerals have antitumor activity in several cancers.<br><br> For instances, arsenic trioxide was known to treat breast cancer and colon cancer cells, selenium was reported to have antitumor potential in several cancers such as colon, prostate, zinc was reported to have potential thera peutic for chemoresistant ovarian cancer and also cadmium induced mitogenic signaling in breast cancer cell by an ER alpha dependent Lenalidomide 分子量 mechanism, Similarly, in the present study, mineral Mica showed antitumor potential in colorectal cancers. Though STB HO exerted anti proliferative activity in HCT116, SW620 and HCT15 colorectal cancer cells, HCT116 cells are were more susceptible to STB HO compared to two other colon cancer cells, since they are positive for transforming growth factor beta 1 and beta 2 expression with a mutation in codon 13 of the ras protooncogene, Also, STB HO increased G1 cell population in a time and concentration dependent manner and enhanced the expression of p21, p27, p53 as cyclin dependent kinase inhibitors, attenuated the expression of proliferating cell nuclear antigen and cyclin D1, implying G1 arrest leading to cell death by STB HO in HCT116 cells.<br><br> Furthermore, STB HO attenuated the ex pression of survival gene PCNA and reduced typical angiogenesis marker VEGF production in HCT116 cells, indicating anti proliferative and anti angiogenic supplier LY294002 activity of STB HO in HCT116 cells. VEGF is an important signaling protein involved in both vasculogenesis and angiogenesis.<br><br> As an essential re ceptor protein tyrosine kinase propagating cellular signal transduction processes, VEGFR 2 is a central target for drug discovery against tumor associated angiogenesis, Consistently, STB HO suppressed the phosphorylation of VEGFR2 in HCT116, SW620 and HCT15 cells and also inhibited the VEGF mediated proliferation as well as attenuated the phosphorylation of VEGFR2 and Akt in hu man umbilical vein endothelial cells, strongly demonstrating anti angiogenic activity via inhibition of VEGFR2 signaling. Consistently, ELISA revealed that STB HO reduced the production of VEGF and MMP 9 in HCT116 cells. Nevertheless, it was noteworthy that STB HO suppressed the tumor volume and weight in athymic nude mice inoculated with HCT116 cells at a dose of 50 and 100 mg kg through two animal studies. However, the in vitro effective concentration was high because of poor solubility of STB HO in cell culture study, which should be improved by nanoparticle method, synthesis or new dilution methods in the near future.