Oridonin exhibits anti-angiogenic activity in human umbilical vein endothelial cells by inhibiting VEGF-induced VEGFR-2 signaling pathway.

Oridonin has been found to be a potential anti-angiogenesis agent. However, its functional targets and the underlying mechanisms are still vague. In vitro studies we found that oridonin not only inhibited VEGF-induced cell proliferation, migration and tube formation but also caused G2/M phase arrest and triggered cellular apoptosis in HUVECs. In mechanistic studies revealed that oridonin exhibited the anti-angiogenic potency, at least in part, through the down-regulation of VEGFR2-mediated FAK/MMPs, mTOR/PI3K/Akt and ERK/p38 signaling pathways which led to reduced invasion, migration, and tube formation in HUVECs. Our results could provide evidence that oridonin exerts strong anti-angiogenesis activities via specifically targeting VEGFR2 and its signaling pathway.

Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells by inhibiting PI3K/AKT/mTOR and Ras/Raf pathways.

Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been reported for its antitumor activity on several cancers. However, its effect on human esophageal cancer remains unclear. In this study, we demonstrated that oridonin could inhibit the growth of human esophageal cancer cells both in vitro and in vivo. Oridonin not only suppressed the proliferation, but also induced cell cycle arrest and mitochondrial-mediated apoptosis in KYSE-30, KYSE-150, and EC9706 cells with dose-dependent manner. Further mechanism studies revealed that oridonin led cell cycle arrest in esophageal cancer cells via downregulating cell cycle-related proteins, such as cyclin B1 and CDK2, while upregulating p53 and p21. Oridonin also increased proapoptotic protein Bax and reduced antiapoptotic protein Bcl-2, as well as the increased expression of cleaved caspase-3, -8, and -9. In addition, oridonin treatment could significantly inhibit the PI3K/Akt/mTOR and Ras/Raf signaling pathway. In vivo results further demonstrated that oridonin treatment markedly inhibited tumor growth in the esophageal cancer xenograft mice model. Taken together, these results suggest that oridonin may be a potential anticancer agent for the treatment of esophageal cancer.

Functional graphene oxide as cancer-targeted drug delivery system to selectively induce oesophageal cancer cell apoptosis.

Graphene oxides (GO) is a promising building material to fabricate desired drug delivery system due to its excellent physicochemical properties. In this study, an innovative nano-drug (Ori@GE11-GO) was constructed based on GE11 peptide functionalized GO for targeted delivery of oridonin to realize the specific recognition of tumour cells and enhance anticancer efficiency. GE11 surface modification onto GO significantly increased the cellular uptake of GO in EGFR overexpressed oesophageal cancer cells (KYSE-30 and EC109 cells) than that of normal cells, indicating the EGFR targeting effects of Ori@GE11-GO. The internalized Ori@GE11-GO could accumulate into lysosomes and significantly inhibit the viability of cancer cells. Moreover, Ori@GE11-GO could effectively induce KYSE-30 and EC109 cells cycle arrest, apoptosis, mitochondrial membrane potential (△Ψm) disruption through the activation of apoptotic signalling pathways and the inhibition of EGFR/Ras/Raf/MEK/ERK signalling pathway, showing potential use of Ori@GE11-GO for cancer treatment. Taken together, this study demonstrates a good strategy for the construction of bio-functionalized GO drug delivery nanosystem to improve the cancer targeting efficiency of anticancer medicines.

Chinese herb medicine matrine induce apoptosis in human esophageal squamous cancer KYSE-150 cells through increasing reactive oxygen species and inhibiting mitochondrial function.

Matrine, as a natural alkaloid isolated from the traditional herb medicine sophora flavescens, has been proved to possess excellent biological activities, including anticancer effects. Now, this research aims to assess the anticancer activities and the mechanism of matrine against esophageal cancer cells, we investigated the proliferative inhibition, apoptosis induction, as well as the underlying mechanism of matrine on esophageal cancer KYSE-150 cells. It was found that matrine could suppress KYSE-150 cell proliferation and significantly mediate cell apoptosis in a dose-dependent relation by increasing intracellular reactive oxygen species level and triggering mitochondrial membrane potential disruption. More precise mechanism studies demonstrated that matrine could up-regulate the expression of Bax proteins and down-regulate the expression of Bcl-2 proteins, as well as the activation about caspase-3, 8 and 9 in KYSE-150 cells. The morphological analysis of KYSE-150 cells exhibited that matrine could destroy the F-actin and nuclei structures and induce morphological damage with increased surface height distribution and roughness of cell membrane. These results not only demonstrated the potential anticancer activity mechanism of matrine at nanoscale, but also provide preliminary guidance for the treatment of esophageal cancer using matrine.

Anti-tumor activity evaluation of novel chrysin-organogermanium(IV) complex in MCF-7 cells.

Chrysin (5,7-dihydroxylflavone, Chry) is a natural product extracted from plants, honey, and propolis. In this work, a novel chrysin-organogermanium(IV) complex (Chry-Ge) with enhanced anticancer activities was synthesized, and its potential anticancer effects against cancer cells were measured using various methods. MTT results showed that Chry-Ge had significant inhibition effects on the proliferation of MCF-7, HepG2 and Colo205 human cancer cell lines in a dose-dependent manner while had little cytotoxic effects on MCF-10A human normal cells (MCF-10A cells) with the same treatment of Chry-Ge. These results suggested that Chry-Ge possessed enhanced anticancer effects and high selectivity between cancer cells and normal cells. The immuno-staining results showed that the nuclei of MCF-7 cells represented a total fragmented morphology and a disorganized cytoskeletal network in MCF-7 cells after Chry-Ge treatment. Besides, atomic force microscopy (AFM) was applied to detect the changes of ultrastructural and biomechanical properties of MCF-7 cellular membrane induced by Chry-Ge. The AFM data indicated that Chry-Ge treatment directly caused the decrease of cell rigidity and adhesion force of MCF-7 cells, suggesting that membrane toxicity might be one of the targets for Chry-Ge in MCF-7 cells. Moreover, the fluorescence-based flow cytometric analysis demonstrated that Chry-Ge could induce apoptosis in MCF-7 cells in ROS-dependent mitochondrial pathway. All results collectively showed that Chry-Ge could be as a promising anticancer drug for cancer therapy.

A label-free electrochemiluminescence cytosensors for specific detection of early apoptosis.

A novel electrochemiluminescence (ECL) cytosensors was developed for the detection of early apoptotic cells by the specific interaction between Annexin V and phosphatidylserine(PS) based on ECL signal of CdS-QDs. Immobilization of Annexin V on a L-cysteine-capped CdS-QDs/Polyaniline nanofibers (PANI-NF) resulted in the stable and high loading of Annexin V on the sensor surface and the possibility of sensitivity enhancement. Early apoptotic cells showed an increased exposure of PS on the cell membrane caused by physiological and pathological response reactions, leading to a strong interaction between the apoptotic cells and the sensor surface, which could be probed by the ECL. Using a real of early apoptotic HepG2 cell induced by resveratrol (RVL), the proposed novel strategy has demonstrated its simplicity, high sensitivity, good selectivity and high reproducibility and label-free capability which might hold a great potential for rapid detection of cell apoptosis and drug screening. The results from this approach have showed good agreement with those obtained using inverted microscope, flow cytometry(FCM) and Atomic force microscopy(AFM). The linear range for early apoptotic cells detection ranged from 500 to 1.0 × 10(6) cells mL(-1) with a detection limit of 500 cells mL(-1). The reported strategy has provided a promising platform for highly sensitive cytosensing and convenient screening of some clinically anticancer drugs.