Low molecular weight fucoidan : preparation and anticancer activities
學生姓名:
劉莉敏
指導教授:
黃意真
學期:
105下
摘 要:
Fucoidan (Fu) is a naturally occurring sulfated polysaccharide extracted from marine brown seaweeds. It has a wide spectrum of activity in biological systems. The biological activities of Fu are closely related to their molecular weight. The aim of this study is to investigate anticancer activities of low molecular weight fucoidan (LMWF). First, the LMWF was prepared by gamma-irradiation. By gamma-irradiated, the molecular weight rapidly dropped to 38 kDa when the sample was irradiated at 10 kGy, then gradually dropped to 7 kDa without the significant elimination of the sulfate groups. LMWF had high cytotoxicity than native fucoidan in cancer cells, such as AGS, MCF-7, and HepG-2. In addition, LMWF showed higher inhibitory activity of cell transformation, resulting in high anticarcinogenicity. The effect of LMWF on apoptosis in MDA-MB-231 cells was investigated in the second study. LMWF induced a time- and dose-dependent increase in the percentage of apoptotic cells and had caused nuclear shrinkage and fragmentation, suggesting that the cytotoxic effect of LMWF on MDA-MB-231 cells was mediated through the induction of apoptosis. That cytochrome c was released from the mitochondria and accumulated in the cytosol of LMWF-treated cells in a time-dependent manner. LMWF caused a decrease in ΔΨm in the MDA-MB-231 cells, as was evident from a reduction in the percentage of cells with high fluorescence intensity. After the LMWF treatment of MDA-MB-231 cells found a time-dependent decrease in the expression of Bcl-2, Mcl-1, and Bcl-xl. Flow cytometric analysis which showed that treating with LMWF for 3 h significantly elevated the intracellular Ca2+ level. LMWF induced cleavage of 280-kDa α-spectrin to 150/145-kDa and 120-kDa breakdown products and indicated that LMWF-induced apoptosis was calpain dependent. In conclusion, these findings of the work suggested that LMWF had better anticancer activity.