• VOSviwer
• bibliometrics
• citespace
• the R programming language

• Humans
• Bibliometrics
• Databases, Factual
• China
• Drugs, Chinese Herbal/therapeutic use

• 2021340104003257 Study on the Medicinal Resources of 40 Standard Varieties of Formula Granules including Vincetoxicum glaucescens in Guangdong Province

• antitumor
• carrier
• drug delivery system
• nanoparticle
• oridonin

• ORI
• anticancer properties
• cancer treatment
• diterpenoid
• natural compound

• Antioxidant
• Chloroform extract
• Cytotoxicity
• Digenea simplex
• Nanosuspension

• Betulin
• Imaging flow cytometry
• In situ
• Nanosuspension
• Triple negative breast cancer

• Eudragit S100
• Simvastatin
• colon targeting
• ethyl cellulose
• nanosuspension

• LY294002
• apoptosis
• breast cancer
• cell cycle
• synergism
• tamoxifen

• Breast Neoplasms/drug therapy
• Breast Neoplasms/metabolism
• Caspases/metabolism
• Cell Cycle Checkpoints/drug effects
• Cell Survival/drug effects
• Chromones/pharmacology
• Cyclin-Dependent Kinase Inhibitor p21/metabolism
• Dose-Response Relationship, Drug
• Drug Synergism
• Female
• Gene Expression Regulation, Neoplastic/drug effects
• Humans
• Inhibitory Concentration 50
• MCF-7 Cells
• Morpholines/pharmacology
• Tamoxifen/pharmacology
• Tumor Suppressor Protein p53/metabolism

• Oridonin
• bioavailability
• biological activity
• formulations
• solubility
• structural modification

• Anti-Inflammatory Agents/chemistry
• Anti-Inflammatory Agents/pharmacokinetics
• Antineoplastic Agents, Phytogenic/chemistry
• Antineoplastic Agents, Phytogenic/pharmacokinetics
• Biological Availability
• Diterpenes, Kaurane/chemistry
• Diterpenes, Kaurane/pharmacokinetics
• Humans
• Solubility
• Tissue Distribution

• BS2014YY047 Shandong Provincial Natural Science Foundation, China

• anti-cancer drugs
• breast cancer
• melanoma
• melatonin analogues
• melatonin receptors

The current agents used for renal cell carcinoma (RCC) only exhibit the moderate response rate among patients. Development of drug resistance eventually fuels the need of either more potent drugs or new drugs to target the resistant pathways. Oridonin is a diterpenoid isolated from the Chinese medicinal herb Rabdosia rubescens and has been shown to have antitumor activities in many cancers. We previously developed new synthetic methodologies to modify structurally diversified diterpenoids and designed a series of nitrogen-enriched oridonin analogs. In this study, we screened a variety of oridonin analogs based on their cytotoxicity using MTT assay and identify the most potent candidate, namely, CYD-6-17. CYD-6-17 exhibited a high potency to inhibit the in vitro growth of several drug-resistant RCC cells as well as endothelial cells stimulated by tumor cells at nanomolar range. Delivery of CYD-6-17 significantly inhibited RCC tumor growth using xenograft model. Mechanistically, it targeted the 3-phosphoinositide-dependent protein kinase 1 gene that appeared to be a potent regulator of AKT and was associated with patient survival after targeted therapies. This offers a new rational therapeutic regimen of CYD-6-17 to drug-resistant RCC based on its novel mechanism of action.

Cell-in-cell structures are created by one living cell entering another homotypic or heterotypic living cell, which usually leads to the death of the internalized cell, specifically through caspase-dependent cell death (emperitosis) or lysosome-dependent cell death (entosis). Although entosis has attracted great attention, its occurrence is controversial, because one cell line used in its study (MCF-7) is deficient in caspase-3.

We investigated this issue using MCF-7 and A431 cell lines, which often display cell-in-cell invasion, and have different levels of caspase-3 expression. Cell-in-cell death morphology, microstructures, and signaling pathways were compared in the two cell lines.

Our results confirmed that MCF-7 cells are caspase-3 deficient with a partial deletion in the CASP-3 gene. These cells underwent cell death that lacked typical apoptotic properties after staurosporine treatment, whereas caspase-3-sufficient A431 cells displayed typical apoptosis. The presence of caspase-3 was related neither to the lysosome-dependent nor to the caspase-dependent cell-in-cell death pathway. However, the existence of caspase-3 was associated with a switch from lysosome-dependent cell-in-cell death to the apoptotic cell-in-cell death pathway during entosis. Moreover, cellular hypoxia, mitochondrial swelling, release of cytochrome C, and autophagy were observed in internalized cells during entosis.

The occurrence of caspase-independent entosis is not a cell-specific process. In addition, entosis actually represents a cellular self-repair system, functioning through autophagy, to degrade damaged mitochondria resulting from cellular hypoxia in cell-in-cell structures. However, sustained autophagy-associated signal activation, without reduction in cellular hypoxia, eventually leads to lysosome-dependent intracellular cell death.

• Autophagy
• Caspase 3
• Cell hypoxia
• Entosis
• MCF-7 cells

Oridonin has attracted considerable attention in the last decade because of its anti-cancer pharmacological properties. This ent-kaurane diterpenoid, isolated from the Chinese herb Rabdosia rubescens and some related species, has demonstrated great potential in the treatment profile of many diseases by exerting anti-tumor, anti-inflammatory, pro-apoptotic, and neurological effects. Unfortunately, the mechanisms via which oridonin exerts these effects remain poorly understood. This review provides an overview of the multifunctional effects of oridonin as well as the reasons for its potential for investigations in the treatment of many diseases other than cancer.

• Antisolvent nanoprecipitation
• Breast cancer
• In-vitro anticancer activity
• Multi-inlet vortex mixer (MIVM)
• Nanoparticles
• Ursolic acid

• Antineoplastic Agents/chemistry
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Cell Cycle/drug effects
• Chemical Precipitation
• Drug Stability
• Female
• Humans
• MCF-7 Cells
• Microscopy, Electron, Transmission
• Nanoparticles/chemistry
• Particle Size
• Reproducibility of Results
• Solubility
• Solvents/chemistry
• Surface Properties
• Suspensions/chemistry
• Suspensions/pharmacology
• Triterpenes/chemistry
• Triterpenes/pharmacology
• Ursolic Acid

• Amoitone B
• Cytotoxicity
• Flow cytometry
• Nanocrystals
• Tissue distribution

• Administration, Intravenous
• Animals
• Antineoplastic Agents/pharmacokinetics
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Area Under Curve
• Cell Death/drug effects
• Cell Line, Tumor
• Cell Shape/drug effects
• Flow Cytometry
• G1 Phase Cell Cycle Checkpoints/drug effects
• Humans
• Inhibitory Concentration 50
• Mice
• Nanoparticles/chemistry
• Nanoparticles/ultrastructure
• Particle Size
• Phenylacetates/chemistry
• Phenylacetates/pharmacokinetics
• Phenylacetates/pharmacology
• Tissue Distribution/drug effects

AIM: To investigate the effect and mechanism of oridonin on the gastric cancer cell line HGC-27 in vitro.

METHODS: The inhibitory effect of oridonin on HGC-27 cells was detected using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. After treatment with 10 μg/mL oridonin for 24 h and 48 h, the cells were stained with acridine orange/ethidium bromide. The morphologic changes were observed under an inverted fluorescence microscope. DNA fragmentation (a hallmark of apoptosis) and lactate dehydrogenase activity were examined using DNA ladder assay and lactate dehydrogenase-release assay. After treated with oridonin (0, 1.25, 2.5, 5 and 10 μg/mL), HGC-27 cells were collected for anexin V-phycoerythrin and 7-amino-actinomycin D double staining and tested by flow cytometric analysis, and oridonin- induced apoptosis in HGC-27 cells was detected. After treatment with oridonin for 24 h, the effects of oridonin on expression of Apaf-1, Bcl-2, Bax, caspase-3 and cytochrome c were also analyzed using reverse-transcript polymerase chain reaction (RT-PCR) and Western blotting.

RESULTS: Oridonin significantly inhibited the proliferation of HGC-27 cells in a dose- and time-dependent manner. The inhibition rates of HGC-27 treated with four different concentrations of oridonin for 24 h (1.25, 2.5, 5 and 10 μg/mL) were 1.78% ± 0.36%, 4.96% ± 1.59%, 10.35% ± 2.76% and 41.6% ± 4.29%, respectively, which showed a significant difference (P < 0.05). The inhibition rates of HGC-27 treated with oridonin at the four concentrations for 48 h were 14.77% ± 4.21%, 21.57% ± 3.75%, 30.31% ± 4.91% and 61.19% ± 5.81%, with a significant difference (P < 0.05). The inhibition rates of HGC-27 treated with oridonin for 72 h at the four concentrations were 25.77% ± 4.85%, 31.86% ± 3.86%, 48.30% ± 4.16% and 81.80% ± 6.72%, with a significant difference (P < 0.05). Cells treated with oridonin showed typical apoptotic features with acridine orange/ethidium bromide staining. After treatment with oridonin, the cells became round, shrank, and developed small buds around the nuclear membrane while forming apoptotic bodies. Lactate dehydrogenase (LDH) release assay showed that after treated with 1.25 μg/mL and 20 μg/mL oridonin for 24 h, LDH release of HGC-27 caused by apoptosis increased from 22.94% ± 3.8% to 52.68% ± 2.4% (P < 0.001). However, the change in the release of LDH caused by necrosis was insignificant, suggesting that the major cause of oridonin-induced HGC-27 cell death was apoptosis. Flow cytometric analysis also revealed that oridonin induced significant apoptosis compared with the controls (P < 0.05). And the apoptosis rates of HGC-27 induced by the four different concentrations of oridonin were 5.3% ± 1.02%, 12.8% ± 2.53%, 28.5% ± 4.23% and 49.6% ± 3.76%, which were in a dose-dependent manner (P < 0.05). After treatment for 24 h, DNA ladder showed that oridonin induced a significant increase in DNA fragmentation in a dose-dependent manner. RT-PCR revealed that mRNA expression levels were up-regulated compared with the controls in caspase-3 (0.917 ± 0.103 vs 0.357 ± 0.019, P < 0.05), cytochrome c (1.429 ± 0.111 vs 1.002 ± 0.014, P < 0.05), Apaf-1 (0.688 ± 0.101 vs 0.242 ± 0.037, P < 0.05) and Bax (0.856 ± 0.101 vs 0.278 ± 0.027, P < 0.05) (P < 0.05), whereas down-regulated in Bcl-2 (0.085 ± 0.012 vs 0.175 ± 0.030, P < 0.05). Western blotting analysis also confirmed this result.

CONCLUSION: Apoptosis of HGC-27 induced by oridonin may be associated with differential expression of Apaf-1, caspase-3 and cytochrome c, which are highly dependent upon the mitochondrial pathway.

• Oridonin
• Gastric cancer
• Proliferation
• Apoptosis
• Apaf-1/caspase-3/cytochrome C