In anti-cancer drug (candidate) screening, there is the need for evaluation at physiological concentrations similar to in vivo. This is often performed by three-dimensionally (3D) cultured cells; however, it requires a long culture period of 2-4 weeks with tedious experimental procedures. Here, we report on a high precision surface plasmon resonance (HP-SPR)-3D system. We developed the system with average fluctuation of 50 ndeg s-1 using two-dimensionally cultured cells attached onto a sensor chip by applying collagen on the top to change their activity into in vivo-like conditions without cell division. It allowed in vivo-like phenotypic screening for anti-cancer drugs within 1 h of drug addition. The data were collected as the stable linear signal change parts for at least 5 min after 25 min following drug addition. The results provided compatibility to clinically related chemosensitivity test for anti-cancer (P <0.001) using two cell lines of pancreatic cancer and three anti-cancer drugs to represent differences in individual gene expression and drug mode of action.
Anti-cancer effect has been reported in oral administration of grape seed extract (GSE) although the clinical trial failed because of its toxicity. Grape seeds should be toxic to prevent them to be eaten by animals. However, once they wake up, they change the ingredients into a form which dissolves easily in water and break toxicity substances inhibiting germination. In order for seeds to sprout and grow, a lot of nutrients as well as life itself reside. The objective of this study is to determine the in vivo-like efficacy and toxicity on anti-cancer and pro-immunity of rapid and synchronized dormancy-broken grape seed endosperm (RSDB-GSE) by our proprietary Grandir recipe. It was performed in case of oral administration using digested and absorbed RSDB-GSE. Direct killing efficacy against all cancer cells was observed in a dose-dependent manner at 2.5 mg/ml or more, and it was the maximum at 5.0 mg/ml for pancreas and liver and at 7.5 mg/ml for breast. The cell viability was less than 20%. At concentrations higher than these, it showed toxicity which was thought to be cell functional shutdown by suspension of mitochondrial polarization. No effect was observed for normal cells. The RSDB-GSE showed general direct cancer killing efficacy for organs. T lymphocytes cytotoxic activity by NK cells was observed in a dose-dependent manner at 3.75 mg/ml or more, and it was kept at least until 5.0 mg/ml. From this, pro-immunity was shown by RSDB-GSE. Consequently, it is expected to express synergistic anti-cancer effect, even orally administered.
One hour in vivo-like phenotypic screening system for anti-cancer drugs using a high precision surface Plasmon resonance device 2 Conventional technology Emerging technology Angle (degree)
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