Xanthatin suppresses pancreatic cancer cell growth via the ROS/RBL1 signaling pathway: In vitro and in vivo insights.

BACKGROUND: As a malignant digestive system tumor, pancreatic cancer has a high mortality rate. Xanthatin is a sesquiterpene lactone monomer compound purified from the traditional Chinese herb Xanthium strumarium L. It has been reported that Xanthatin exhibits inhibitory effects on various cancer cells in retinoblastoma, glioma, hepatoma, colon cancer, lung cancer, as well as breast cancer. However, in pancreatic cancer cells, only one report exists on the suppression of Prostaglandin E2 synthesis and the induction of caspase 3/7 activation in Xanthatin-treated MIA PaCa-2 cells, while systematic in vitro and in vivo investigations and related mechanisms have yet to be explored. PURPOSE: This research aims to explore the in vitro and in vivo effects of Xanthatin on pancreatic cancer and its molecular mechanisms. METHODS: The anticancer effects and mechanisms of Xanthatin on pancreatic cancer cells were assessed through employing cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) assay, carboxyfluorescein diacetate succinimidyl ester (CFDA SE) cell proliferation assay, colony formation assay, wound healing assay, transwell assay, Annexin V-FITC/propidium iodide (PI) dual staining, Hoechst nuclear staining, Western blot analysis, phosphoproteomics, and reactive oxygen species (ROS) measurement. The in vivo anticancer effects of Xanthatin on pancreatic cancer cells were studied using a nude mouse model. RESULTS: The present study showed that Xanthatin can prevent the proliferation and metastasis of pancreatic cancer cells and trigger the exposure of phosphatidylserine (PS), chromatin condensation, and caspase activation, thereby inducing apoptosis. Phosphoproteomic analysis indicated that Xanthatin inhibits the phosphorylation of the proliferation-associated protein RBL1, and oxidative stress can lead to RBL1 dephosphorylation. Further investigation revealed that Xanthatin significantly upregulates ROS levels in pancreatic cancer cells, and the antioxidant N-acetylcysteine (NAC) can reverse Xanthatin-induced cell proliferation inhibition and apoptosis. In addition, Xanthatin can suppress pancreatic cancer cell growth in a xenograft nude mouse model with low toxicity to the mice. CONCLUSION: Xanthatin may inhibit the proliferation of pancreatic cancer cells and trigger apoptosis through the ROS/RBL1 signaling pathway.

Christensenella regulated by Huang-Qi-Ling-Hua-San is a key factor by which to improve type 2 diabetes.

There is a lot of evidence that oral hypoglycemic drugs work by affecting gut microbes, but the key strains responsible for this effect are not well known. Huang-Qi-Ling-Hua-San (HQLHS), composed of Astragalus Membranaceus, Ganoderma lucidum, Inonotus obliquus, and Momordica charantia L., is a specially designed Chinese medicine formula to treat type 2 diabetes (T2D). In this study, a mouse model of T2D induced by high-fat diet and streptozotocin was used to explore the mechanism of HQLHS in improving hyperglycemia and hyperlipidemia through multiple rounds of animal experiments, such as HQLHS feeding, fecal microbiota transplantation (FMT), and live bacteria feeding, so as to explore the potential target intestinal flora in its hypoglycemic effect. Results show that such specific taxa as Bifidobacterium, Turicibacter, Alistipes, Romboutsia, and Christensenella were identified to be preferably enriched by HQLHS and then assumed to be the target microbes. Herein, FMT was used to test if the upregulated beneficial bacteria by HQLHS play a therapeutic role. The strain Christensenella minuta DSM 22607 and the strain Christensenella timonensis DSM 102800 were selected to test the beneficial effect of Christensenella taxa on T2D. Diabetic animals supplemented with these strains showed the improvement in blood glucose and lipid metabolism, the promotion of GLP-1 secretion, the increase in antioxidant capacity, the inhibition of hepatic gluconeogenesis, the suppression of intestinal glucose absorption, the enhancement of intestinal barrier, reduced LPS-induced inflammation, and the reduction of branched amino acids (BCAAs) content in the liver. Overall, these data demonstrate that Christensenella plays a beneficial role in T2D and is a target for the action of HQLHS therapy.

Monitoring of the bacterial and fungal biodiversity and dynamics during Massa Medicata Fermentata fermentation.

The microbial community dynamics play an important role during Massa Medicata Fermentata (MMF) fermentation. In this study, bacterial and fungal communities were investigated based on the culture-dependent method and polymerase chain reaction-denaturing gradient gel electrophoresis analysis. Meanwhile the dynamic changes of digestive enzyme activities were also examined. Plating results showed that MMF fermentation comprised two stages: pre-fermentation stage (0-4 days) was dominated by bacterial community and post-fermentation stage (5-9 days) was dominated by fungal community. The amount of bacteria reached the highest copy number 1.2 × 10(10) CFU/g at day 2, but the fungi counts reached 6.3 × 10(5) CFU/g at day 9. A total of 170 isolates were closely related to genera Enterobacter, Klebsiella, Acinetobacter, Pseudomonas, Mucor, Saccharomyces, Rhodotorula, and Amylomyces. DGGE analysis showed a clear reduction of bacterial and fungal diversity during fermentation, and the dominant microbes belonged to genera Enterobacter, Pediococcus, Pseudomonas, Mucor, and Saccharomyces. Digestive enzyme assay showed filter paper activity; the activities of amylase, carboxymethyl cellulase, and lipase reached a peak at day 4; and the protease activity constantly increased until the end of the fermentation. In this study, we carried out a detailed and comprehensive analysis of microbial communities as well as four digestive enzymes' activities during MMF fermentation process. The monitoring of bacterial and fungal biodiversity and dynamics during MMF fermentation has significant potential for controlling the fermentation process.