Cinobufacini is a well-known Chinese medicine extracted from Venenum Bufonis, also called Chan Su. It has been used clinically for various cancers, including colon cancer. However, the function of Cinobufacini on colon cancer invasion and metastasis, and its underlying molecular mechanism, is still not clear. In this study, we investigated the function and mechanism of Cinobufacini on colon cancer invasion and metastasis both in vitro and in vivo studies. Human colon cancer cells were cultured. CCK assay was used to detect the effect of Cinobufacini on colon cancer cells proliferation. The invasion and migration abilities were observed by transwell assays, and the expression of invasion and migration related genes MMP2, MMP9, and epithelial-to-mesenchymal transition (EMT) relate genes were observed by Western blot assays. An orthotopic xenograft model in nude mice was established using colon cancer HCT116 cells, and the function of Cinobufacini on colon cancer invasion and metastasis were observed in vivo. We found Cinobufacini significantly inhibited colon cancer cell proliferation in a dose/time-dependent manner; the invasion and migration abilities of colon cancer were decreased after treated with Cinobufacini. The metastasis and EMT related genes MMP9, MMP2, N-cadherin and Snail were obviously down-regulated, while the expression of E-cadherin was up-regulated after treatment with Cinobufacini. The Wnt/[Formula: see text]-catenin signaling pathway related genes were observed using WB,and results show that the expression of [Formula: see text]-catenin, wnt3a, c-myc, cyclin D1, and MMP7 were all down-regulated after being treated with cinobufacini, while the expression of APC was up-regulated. In vivo studies of the volume and weight of orthotopic xenograft tumors showed significantly shrinkage in the Cinobufacini group compared to the control group. The enterocoelia and liver metastasis tumors were significantly decreased, and the expression of MMP9, MMP2, and [Formula: see text]-catenin were also down-regulated, while E-cadherin was up-regulated in vivo after the treatment with Cinobufacini. Our data proves that Cinobufacini can inhibit colon cancer invasion and metastasis both in vitro and in vivo; the mechanism is related by suppressing the Wnt/[Formula: see text]-catenin signaling pathway and then inhibiting the EMT of CRC.
Three
typical edible oils (palm oil, PO; leaf lard oil, LO; rapeseed
oil, RO) and triacylglycerols (TAGs) (glycerol tripalmitate, GTP;
glycerol tristearate, GTS; glycerol trioleate, GTO) were selected
to conduct digestion experiments using fully designed in vitro digestion
model. The evolutions in mean particle diameter, ζ-potential,
and microstructural changes during different digestion stages were
investigated. Free fatty acid (FFA) release extent and kinetics were
monitored by pH-Stat method. The particle characterization of different
lipids during passage through the GIT depended on lipid type and the
microenvironment they encountered. Absorbed surface protein can hardly
be the obstacle for pancreas lipase to catalyze lipid hydrolysis after
gastric digestion. The maximum FFA release level and apparent rate
constant in small intestine digestion stage of the three oils and
TAGs were: PO > RO > LO, GTP > GTS > GTO, respectively.
PO showed
the highest FFA release level and rate mainly due to the short chain
length saturated palmitic acid (C16:0) specifically located in the
Sn-1, 3 positions of TAG molecules in palm oil, while the Sn-1, 3
positions of TAG molecules in RO and LO were mainly mono- or polyunsaturated
fatty acids (C18:1 or C18:2), restricting the continuous hydrolysis
reaction. These findings can provide some basic understanding of the
digestion differences of different lipids, which may be useful for
their nutritional and functional evaluation and the applicability
in the food area.
Alzheimer’s disease (AD) is the most common cause of dementia, affecting more than 10% of people over the age of 65. Age is the greatest risk factor for AD, although a combination of genetic, lifestyle and environmental factors also contribute to disease development. Common features of AD are the formation of plaques composed of beta-amyloid peptides (Aβ) and neuronal death in brain regions involved in learning and memory. Although Aβ is neurotoxic, the primary mechanisms by which Aβ affects AD development remain uncertain and controversial. Mouse models overexpressing amyloid precursor protein and Aβ have revealed that Aβ has potent effects on neuroinflammation and cerebral blood flow that contribute to AD progression. Therefore, it is important to consider how endogenous signaling in the brain responds to Aβ and contributes to AD pathology. In recent years, Aβ has been shown to affect ATP release from brain and blood cells and alter the expression of G protein-coupled P2Y receptors that respond to ATP and other nucleotides. Accumulating evidence reveals a prominent role for P2Y receptors in AD pathology, including Aβ production and elimination, neuroinflammation, neuronal function and cerebral blood flow.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.