Abstract
BackgroundThough Mica, a thin and sheet like mineral, has been used as a mineral medicine for treatment of bleeding, dysentery and inflammation in traditional medicine including Ayurveda, the biological evidences of Mica were not clearly elucidated so far. Thus, in the present study, the antitumor mechanism of particled Mica (STB-HO) was examined in colorectal cancers.MethodsAthymic nude mice were inoculated with HCT116 colon cancer cells and orally administered STB-HO daily for 41 days, and HCT116 and human umbilical vein endothelial cells (HUVECs) were treated with STB-HO for 0 ~ 24 hours to perform immunoblotting, cytotoxicity assay, FACs analysis and measurement of matrix metalloproteinase 9 (MMP-9) secretion and other experiments. Significant differences of all date were evaluated using Student’s t-test and a Turkey-Kramer multiple-comparison post test.ResultsSTB-HO significantly suppressed the tumor volume and weight in athymic nude mice inoculated with HCT116 cells at a dose of 100 mg/kg. Thus, the in vivo antitumor mechanism of STB-HO was to elucidated in vitro as well. STB-HO exerted cytotoxicity in HCT116, SW620 and HCT15 colorectal cancer cells. Also, STB-HO increased G1 cell population in a time and concentration dependent manner, enhanced the expression of p21, p27, p53 as cyclin dependent kinase (CDK) inhibitors, attenuated the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 and also reduced the production of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) in HCT116 cells. Consistently, STB-HO suppressed the phosphorylation of VEGFR2 in HCT116, SW620 and HCT15 cells. Also, STB-HO inhibited the VEGF mediated proliferation and also attenuated the phosphorylation of VEGFR2 and Akt in human umbilical vein endothelial cells (HUVECs).ConclusionsCollectively, these findings suggest that STB-HO has chemopreventive potential via G1 arrest and inhibition of proliferation and VEGFR2 in HCT116 colorectal cancer cells.
Highlights
Though Mica, a thin and sheet like mineral, has been used as a mineral medicine for treatment of bleeding, dysentery and inflammation in traditional medicine including Ayurveda, the biological evidences of Mica were not clearly elucidated so far
STB-HO inhibits cell proliferation in human colorectal cancer cell lines We first investigated whether STB-HO can suppress the proliferation of human colon cancer cell lines
We found that the phosphorylation of pVEGFR2, PI3K and pAKT was attenuated in three colon cancer cells by STB-HO (Figure 5B), demonstrating STB-HO can abrogate the activity of proliferation in cancer cells via suppression of pVEGFR2, PI3K and pAKT
Summary
Though Mica, a thin and sheet like mineral, has been used as a mineral medicine for treatment of bleeding, dysentery and inflammation in traditional medicine including Ayurveda, the biological evidences of Mica were not clearly elucidated so far. In the present study, the antitumor mechanism of particled Mica (STB-HO) was examined in colorectal cancers. Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. Chemotherapy including 5-fluorouracil (5-FU) therapy and surgical resection are well known methods for colon cancer treatment [1]. Recently natural products [3] and compounds [4,5,6] were reported to have antitumor effects in colorectal cancers alone or in combination with anticancer agents [7] with low toxicity. There are evidences that mineral selenium has antitumor activity in colon cancers [9,10,11,12]
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