Sesquilignans PD from Zanthoxylum nitidum var. tomentosum exerts antitumor effects via the ROS/MAPK pathway in liver cancer cells.

Sesquilignans PD is a natural phenylpropanoid compound that was isolated from Zanthoxylum nitidum var. tomentosum. In this study, we assessed the antitumor effect of PD on SK-Hep-1 and HepG2 cells and the underlying molecular mechanisms. The results revealed that PD markedly inhibited the proliferation and migration of both liver cancer cells. Moreover, PD induced apoptosis, autophagy, and reactive oxygen species (ROS) production in liver cancer cells. Notably, PD increased the protein levels of p-p38 MAPK and p-ERK1/2 in liver cancer cells. This is the first report on the anticancer effect of PD, which is mediated via increased ROS production and MAPK signaling activation.

Discovery of novel 2-oximino-2-indolylacetamide derivatives as potent anticancer agents capable of inducing cell autophagy and ferroptosis.

A series of 2-oximino-2-indolylacetamide derivatives were designed, synthesized and evaluated for their antitumour effects. Among them, 4d exhibited the most potent antiproliferative effect in vitro on the tested human cancer cells. Additionally, 4d significantly induced cell apoptosis, caused mitochondrial dysfunction, promoted Bax, cleaved-PARP and p53 expression and inhibited Bcl-2 expression in 5-8F cells. Moreover, 4d remarkably promoted autophagosome formation, leading to cell apoptosis. Further investigation indicated that 4d could trigger cell death through cell ferroptosis, including increased ROS generation and lipid peroxidation and decreased glutathione peroxidase 4 (GPx4) expression and glutathione (GSH) levels. More importantly, 4d induced 5-8F cell death by activating ROS/MAPK and inhibiting the AKT/mTOR and STAT3 signalling pathways. Interestingly, 4d significantly suppressed tumour growth in a 5-8F cell xenograft model without obvious toxicity to mice. Overall, these results demonstrate that 4d may be a potential compound for cancer therapy.

Alkaloids from Corydalis saxicola and their antiproliferative activity against cancer cells.

Eight undescribed alkaloids named corydalisine D-K (1-7), including one isoquinoline benzopyranone alkaloid (1), one benzocyclopentanone alkaloid (2), four benzofuranone alkaloids (3, 4, and 5a/5b) and two protoberberine alkaloids (6 and 7), along with fourteen known ones, were isolated from the Corydalis saxicola. Their structures, including absolute configurations, were unambiguously identified using spectroscopic techniques, single-crystal X-ray diffraction and electron circular dichroism calculation. Compounds 2, 14 and 21 exhibit antiproliferative activity against five cancer cell lines. The aporphine alkaloid demethylsonodione (compound 14), which exhibited the best activity (IC50 = 3.68 ± 0.25 µM), was subjected to further investigation to determine its mechanism of action against the T24 cell line. The molecular mechanism was related to the arrest of cell cycle S-phase, inhibition of CDK2 expression, accumulation of reactive oxygen species (ROS), induction of cell apoptosis, inhibition of cell migration, and activation of p38 MAPK signaling pathway. The results indicated that 14 could be used as a potential candidate agent for further development of anti-bladder transitional cell carcinoma.

Pentagalloylglucose suppresses the growth and migration of human nasopharyngeal cancer cells via the GSK3ß/ß-catenin pathway in vitro and in vivo.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of malignant squamous cell tumour originating from the nasopharynx epithelium. Pentagalloylglucose (PGG) is a natural polyphenolic compound that exerts anticancer effects in many types of tumours. However, the role and underlying mechanism of PGG in NPC cells have not been fully defined. PURPOSE: This study aimed to investigate the anticancer activity of PGG as well as the potential mechanism in NPC cells. METHODS: The effects of PGG on the proliferation, apoptosis and cell cycle distribution of CNE1 and CNE2 cells were assessed by MTT and flow cytometry assays. Cell migration was evaluated using wound healing and transwell assays. The expression of microtubule-associated protein 1 light chain 3 beta (LC3B) was observed by immunofluorescence staining. Western blotting was used to explore the levels of related proteins and signalling pathway components. Furthermore, the effects of PGG on NPC cell growth were analysed in a xenograft mouse model in vivo using cisplatin as a positive control. RESULTS: PGG dose-dependently inhibited the proliferation of CNE1 and CNE2 cells. PGG regulated the cell cycle by altering p53, cyclin D1, CDK2, and cyclin E1 protein levels. PGG induced apoptosis and autophagy in NPC cells and elevated the Bax/Bcl-2 ratio and the protein levels of LC3B. Moreover, PGG decreased NPC cell migration by increasing E-cadherin and decreasing N-cadherin, vimentin and CD44 protein levels. Mechanistically, PGG treatment downregulated p-mTOR and ß-catenin expression but upregulated p-p38 MAPK and p-GSK3ß expression. In addition, PGG significantly inhibited NPC cell tumour growth and lung metastasis in vivo. CONCLUSION: PGG may suppress cell proliferation, induce apoptosis and autophagy, and decrease the metastatic capacity of NPC cells through the p38 MAPK/mTOR and Wnt/ß-catenin pathways. The present study provides evidence for PGG as a potential therapy for NPC.

The neurotrophic and antineuroinflammatory effects of phenylpropanoids from Zanthoxylum nitidum var. tomentosum (Rutaceae).

Three novel lignans (1, 5 and 6) and two novel quinic acids (16 and 17) along with 15 known phenylpropanoids were obtained from the ethanol extract of Zanthoxylum nitidum var. tomentosum (Rutaceae). Their structures were confirmed by comprehensive spectroscopic data (NMR and HRESIMS), and the absolute configurations of all novel compounds were elucidated based on electronic circular dichroism (ECD) spectroscopic data. The production of nitric oxide (NO) in BV-2 microglial cells induced through lipopolysaccharide (LPS) was used to evaluate in vitro anti-neuroinflammatory activity of compounds 1-20. Compound 2, 3, 7 and 16 showed excellent inhibition of LPS-induced NO production. The structure-activity relationships of the isolates were investigated. In addition, the mechanism of action of 2 was elucidated by RT-PCR and Western blotting analysis, which indicated that it reduced neuroinflammatory mainly through NLRP3/caspase1 signaling pathways in LPS-induced BV2 microglial cells.