p-Hydroxylcinnamaldehyde from cochinchinamomordica seed reverses resistance to TRAIL in human oesophageal squamous cell carcinoma via the activation of the p38 mitogen-activated protein kinase signalling pathway.

BACKGROUND: Our previous studies have showed that p-Hydroxylcinnamaldehyde (CMSP) could induce the differentiation of ESCC cells via the cAMP-RhoA-MAPK signalling pathway, which suggests a new potential strategy for ESCC treatment. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in several tumour cells by binding to the death receptors DR4 and DR5. However, TRAIL has little effect on oesophageal squamous cell carcinoma (ESCC) cells due to the loss of the receptors. The present study determined the effect of CMSP, the firstly found chemical constituent of Cochinchinamomordica seed (CMS), on TRAIL-induced apoptosis and its mechanism in ESCC cells. METHODS: MTS assays were performed to examine the CMSP- and TRAIL-mediated inhibition of ESCC cell growth. Flow cytometry and Hoechst 33258 staining assays were used to detect apoptosis in ESCC cells treated with CMSP combined with TRAIL. Western blotting was used to determine the effect of CMSP on the expression of p38, p-p38, DR4, DR5, Bid and caspase-3/8 in ESCC cells treated with CMSP combined with TRAIL. Additionally, immunodeficient Balb-c/null mouse model was used to determine the chemotherapeutic efficacy of CMSP and TRAIL against ESCC tumour xenograft growth in vivo. RESULTS: We found that the combination of CMSP and TRAIL had a greater inhibitory effect on ESCC cell viability in vitro than CMSP or TRAIL alone. CMSP enhanced the TRAIL-induced apoptosis in ESCC cells by upregulating the expression of DR4 and DR5 via the p38 MAPK signalling pathway. Furthermore, the increased expression of DR4 and DR5 upon TRAIL-induced apoptosis in ESCC cells was mediated at least in part by subsequent caspase-3 and caspase-8 activation. Moreover, the in vivo model showed that tumour growth was significantly slower in CMSP and TRAIL combination-treated mice than in mice treated with CMSP or TRAIL alone. CONCLUSION: Taken together, our findings indicate that CMSP as an extract from TCM, might be as a potential sensitizer of TRAIL and thus provide a novel strategy for the clinical treatment of ESCC.

Microscopic and Submicroscopic Gradient Variation of Olfactory Systems among Six Sinocyclocheilus Species Living in Different Environments.

The fish genus Sinocyclocheilus contains many different species that inhabit diverse natural environments, such as surface water layer, cave, or intermediate. As a result of these different habitats there are some differences in their sensory systems. Microscopic and submicroscopic structures of olfactory systems in six representative species of Sinocyclocheilus were studied, including one surface-dwelling species (S. grahami), two intermediate species (S. jii and S. macrophthalmus) and three cave-dwelling species (S. brevibarbatus, S. anshuiensis, and S. tianlinensis). Due to adaptive evolution under extreme environmental conditions, cave-dwelling species have more developed olfactory systems. We observed that, compared with surface-dwelling species, the olfactory sac of the cave-dwelling Sinocyclocheilus species has the following characteristics: higher density of cilia, greater length of sensory cilia, many other special structures (micro-ridge, olfactory islet, rod cilia). These results reveal different levels of olfactory system development, consistent with the view that that cave-dwelling species have more developed olfactory systems than intermediate and surface-dwelling species.