Effect of the polysaccharides derived from Dendrobium officinale stems on human HT-29 colorectal cancer cells and a zebrafish model

Abstract

Human colorectal cancer (CRC) is treated with 5-fluorouracil (5-Fu). However, this drug causes various adverse effects, suggesting the benefit of developing safer natural-based drugs with high specificity and tolerable adverse effects. Dendrobium officinale has been used as a functional food and important medicine in China for more than a thousand years. The natural polysaccharides obtained from D. officinale (DOPW-1) show inhibitory activity against cancer cells. This study aimed to comparatively investigate the anticancer activity of DOPW-1 and mannose (Mann) on HT-29 cells and explored the possible underlying molecular mechanisms of CRC treatment. HT-29 cells were treated with 5-Fu, DOPW-1, and Mann or their combinations. Cell viability and apoptosis were examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Hoechst 33342 with annexin V-fluorescein isothiocyanate/propidium iodide assays, respectively. DOPW-1 showed good antitumor effects on HT-29 cells and significantly potentiated the anticancer activities of 5-Fu in vitro and in vivo. DOPW-1 significantly inhibited tumor metastasis in the zebrafish model. Furthermore, the monosaccharide composition of DOPW-1 might not have an important effect on its antitumor activity. The results of Western blot analysis suggested that DOPW-1 alone and in combination with 5-Fu induced cell apoptosis using the mitochondria-dependent intrinsic apoptotic pathway. Thus, DOPW-1 is a potential source of natural polysaccharides for CRC therapy alone or in combination with 5-Fu.