Overtaking lung cancer,breast cancer is now the most commonly diagnosed cancer seriously threatening people's health and life. As the main effective component of Tripterygium wilfordii,triptolide( TP) has attracted increasing attention due to its multitarget and multi-pathway anti-tumor activity. Recent studies have revealed that breast cancer-sensitive TP enables the inactivation of breast cancer cells by inducing tumor cell apoptosis and autophagy,interfering in tumor cell metastasis,resisting drug resistance,arresting tumor cell cycle,and influencing tumor microenvironment. It has been recognized as a promising clinical antitumor agent by virtue of its widely accepted therapeutic efficacy. This paper reviewed the anti-breast cancer action and its molecular mechanisms of TP on the basis of the relevant literature in the past ten years,and proposed application strategies in view of the inadequacy of TP to provide a reference for further research on the application of TP in the treatment of breast cancer.
Breast Neoplasms/genetics* ; Diterpenes/pharmacology* ; Epoxy Compounds ; Female ; Humans ; Phenanthrenes ; Tumor Microenvironment

OBJECTIVE: To determine the feasibility whether the bovine jugular venous conduit (BJVC) can be fixed with polyepoxy compound (PC). METHODS: Twenty-four BJVCs were divided into 3 groups and fixed with polyepoxy compound (PC group, n = 8), glutaraldehyde (GA group, n = 8), and unfixed group (Control group, n = 8), respectively. The morphologic and mechanical properties of BJVCs in the 3 groups, including thickness, diameter, moisture content, denaturation temperature, tensile strength, elongation at break, and fixation index were measured. The rat subcutaneous model for the assessment of tissue calcification was used. The calcium content in bovine jugular vein patches and valves was determined by flame atomic absorption spectrophotometer. RESULTS: There was no difference in the wall thickness, diameter, and tissue water content between PC and the control group, but significant difference was found between GA and PC groups. The mechanical properties of PC group and GA group were not significantly different, but they were better than those of the control group. GA-fixed BJVC samples showed clear calcification, while PC fixed BJVC were calcified significantly less. CONCLUSION PC is an effective and suitable choice for the treatment of BJVC since it can effectively preserve the structure and the anti-reflow function of valves in bovine jugular vein and it has better anti-calcification properties.
Animals ; Biocompatible Materials ; Bioprosthesis ; Blood Vessel Prosthesis ; Cattle ; Cross-Linking Reagents ; pharmacology ; Epoxy Compounds ; pharmacology ; Jugular Veins ; Polymers

This study was purposed to investigate the effect of triptolide on bortezomib-induced apoptosis in multiple myeloma cell line NCI-H929(H929). MTT assay was applied to detect the inhibitory effects of triptolide and bortezomib alone or combined at different concentrations on H929 cells, the cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI staining. The results showed that both triptolide (10 - 100 ng/ml) and bortezomib (10 - 100 nmol/L) alone or combination inhibited the proliferation of MM cell line H929 in a concentration-dependent manner. The apoptotic rate of H929 cells in group of triptolide combined with bortezomib was much higher than that in groups of single drug or control; moreover, the apoptotic rate of H929 cells treated by non-inhibitory concentration of triptolide (10 ng/ml) combined with bortezomib (40 nmol/L) for 24 h was significantly higher than that by bortezomib alone (P < 0.05). It is concluded that triptolide can significantly enhance the pro-apoptotic activity of bortezomib in MM cells.
Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Humans ; Multiple Myeloma ; pathology ; Phenanthrenes ; pharmacology ; Pyrazines ; pharmacology

The aim of this study was to investigate the anti-proliferation and pro-apoptosis of triptolide on Jurkat cell line in acute T lymphocytic leukemia. The Jurkat cells were treated with various concentrations of triptolide (0, 1, 2, 4, 8, 16 microg/L) for 12 hours. The inhibitory ratio was measured by Cell Counting Kit-8 assay. The effects of triptolide on apoptosis of Jurkat cells were determined by DNA fragmentation (DNA ladder), Hoechst 33258, PI and Annexin V-FITC/PI double staining. The results demonstrated that triptolide inhibited the proliferation of Jurket cells. The 50% inhibitory concentration (IC(50)) was 4.0 microg/L. Chromatin condensation in the cells treated with triptolide could be seen by light microscopy. DNA electrophoresis showed evidence of nuclear fragmentation (DNA ladder). The hypoploid (sub-G(1)) population was increased after treatment with triptolide. The translocation of phosphatidylserine at the outer surface of the cell plasma membrane could be induced by triptolide. After treatment with triptolide for 12 hours, the rates of apoptotic cells were significantly increased. Moreover, these pro-apoptosis effects were in time-dependent manner. It is concluded that triptolide can inhibit the proliferation and induce the apoptosis of Jurkat cells. This study provides experimental basis for clinical use of triptolide in leukemia therapy.
Antineoplastic Agents, Alkylating ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Humans ; Jurkat Cells ; Phenanthrenes ; pharmacology

OBJECTIVETo develop a drug delivery system triptolide-polyethylenimine-cyclodextrin and to evaluate its anticancer activity in vitro.

METHODSTriptolide was conjugated to polyethylenimine-cyclodextrin by N, N'-carbonyldiimidazole to form triptolide-polyethylenimine-cyclodextrin. (1)H-NMR, FT-IR and XRD were used to confirm its structure. The anticancer effect of the polymer was assessed by MTT assay, erasion trace test and hematoxylin-eosin staining. The potential to condense siRNA and to delivery siRNA into cytoplasm was demonstrated by gel retardation assay, zeta-potential determination and fluorescence staining.

RESULTSTriptolide was successfully conjugated to polyethylenimine-cyclodextrin and the conjugation rate of triptolide was 10% (w/w). siRNA was effectively condensed by the polymer at the N/P ratio of 5, and its particle size was 300 ±15 nm and zeta potential was 8 ±2.5 mV. MTT assay, erasion trace test and hematoxylin-eosin staining revealed that triptolide-polyethylenimine-cyclodextrin had anticancer effect and low cytotoxicity to normal cells. The polymer was able to deliver siRNA to the cytoplasm effectively as demonstrated by fluorescence staining.

CONCLUSIONTriptolide-polyethylenimine-cyclodextrin is able to inhibit the growth and migration of cancer cells in vitro and to carry siRNA into cells effectively. It is potential to be used as a novel prodrug for co-delivery of gene and drug in cancer treatment.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Cyclodextrins ; Diterpenes ; administration & dosage ; pharmacology ; Drug Carriers ; Epoxy Compounds ; administration & dosage ; pharmacology ; Humans ; Nanoparticles ; Phenanthrenes ; administration & dosage ; pharmacology ; Polyethyleneimine ; Polymers

Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.
Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Autophagy ; Cell Cycle Checkpoints ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Humans ; Neoplasms ; drug therapy ; Phenanthrenes ; pharmacology ; Tripterygium ; chemistry

As a major active component extracted from traditional Chinese herb Tripterygium wilfordii Hook F, triptolide exhibits multiple pharmacological effects. Autophagy is an evolutionary conserved intracellular catabolic process involved in cytoplasmic materials degradation. Autophagic dysfunction contributes to the pathologies of many human diseases, which makes it a promising therapeutic target. Recent studies have shown that triptolide exerts neuroprotection, anti-tumor activities, organ toxicity, and podocyte protection by modulating autophagy. This article highlights the current information on triptolide-modulated autophagy, analyzes the possible pathways involved, and describes the crosstalk between autophagy and apoptosis modulated by triptolide, in hope of providing implications for the roles of autophagy in pharmacological effects of triptolide and expanding its novel usage as an autophagy modulator.
Animals ; Apoptosis ; drug effects ; Autophagy ; drug effects ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Humans ; Neoplasms ; drug therapy ; pathology ; Neuroprotective Agents ; pharmacology ; Phenanthrenes ; pharmacology ; Podocytes ; drug effects

AIMTo explore the effect of Triptolide on airway remodeling and the expression of Phosphoinositide 3-Kinases in asthmatic rats.

METHODS40 rats were randomly divided into 5 groups (n = 8): (1) Control group; (2) Asthmatic 4 weeks group; (3) Asthmatic 6 weeks group; (4) Therapeutic 4 weeks group; (5) Therapeutic 6 weeks group. The airway resistance and eosinophilic inflammation of airway wall were observed. The airway wall thickness (WA/Pi), the bronchial smooth muscle thickness (smooth muscle area/Pi) and the number of bronchial smooth muscle nucleus (N/Pi) were measured by image analysis system. The expression of PI3K protein and mRNA were determined by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS(1) The expression of PI3K p85alpha protein and mRNA in asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01, P < 0.01 P < 0.05). (2) The WA/Pi, the smooth muscle area/Pi and the N/Pi of asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01). (3) The airway resistance of asthmatic 4 weeks group and asthmatic 6 weeks group were significantly higher than the control group, respectively (P < 0.01). The above-mentioned parameters of therapeutic 6 weeks group were significantly lower than those of asthmatic 4 weeks group, asthmatic 6 weeks group and therapeutic 4 weeks group, respectively (P < 0.01, P < 0.01, P < 0.05).

CONCLUSIONThe proliferation of airway smooth muscle is a remarkable character of airway remodeling in asthma. The PI3K signal pathway may be involved in the process. Triptolide may reduce AHR and decrease the proliferation of ASMCs by inhibiting the expression of PI3K. It may have potential therapeutic effects in the asthmatic airway remodeling.

Airway Remodeling ; Animals ; Asthma ; metabolism ; physiopathology ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Male ; Phenanthrenes ; pharmacology ; Phosphatidylinositol 3-Kinase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

AIMTo investigate the effect of triptolide on proliferation of PC12 cells and the mechanism involved in the effect, and provide evidence for clinical use of triptolide in treatment of tumor.

METHODSBy means of morphological observation, MTT assay, flow cytometry (FCM) and RT-PCR, the effect of triptolide on the proliferation of PC12 cells was observed in vitro.

RESULTSThe proliferation inhibition was found on PC12 cells incubated with triptolide (5 x 10(3) or 25 x 10(3) g/L) for 24 h, 48 h and 72 h, and with the higher concentration of triptolide, the inhibition was stronger. Low concentration of triptolide (1 x 10(3) g/L) showed no significant effect on proliferation of PC12 cells. After treatment of PC12 cells with triptolide (5 x 10(3) g/L) for 24 h, increased percentage of G0-G1 phase and decreased percentage of S phase were found. Expression of translational elongation factor 2A3-2 was reduced after treatment of PC12 cells with triptolide (5 x 10(3) g/L). The expression of 2A3-2 was weaker in PC12 cells treated with triptolide for 48 h than for 24 h.

CONCLUSIONTriptolide inhibits the proliferation of PC12 cells. The inhibition may be realized by changing the expression of 2A3-2 and preventing the transition from G0-G1 phase to S phase.

Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Flow Cytometry ; PC12 Cells ; drug effects ; Phenanthrenes ; pharmacology ; Rats

OBJECTIVETo study the effect of triptolide (TP) on the methylation status of human promyelocytic leukemia cells (HL-60) and explore a preliminary demethylation mechanism.

METHODSNormal HL-60 cells as control group, the cell proliferation level of HL-60 cells was detected by MTT assay, being treated by different concentration TP (3.125, 6.25, 12.5, 25 nmol/L) for 24 h or 48 h respectively; Choosing the 3.125 nmol/L and the 6.25 nmol/L TP affected HL-60 cells for 48 h, the cell apoptosis rate and cell cycle were determined by flow cytometry, the expressions of death-associated protein kinase 1 (DAPK-1) and methyltransferase DNMT1, DNMT3B mRNA were measured by real time-PCR (RT-PCR), LINE-1, DAPK-1 genes'methylation variations were analyzed by methylation specific PCR (MSP).

RESULTSCompared with control group, the different concentration TP could significantly inhibit the proliferation of HL-60 in a time-dose dependent manner (P<0.05, P<0.01). After being treated by TP for 48 h, the cell early apoptosis rate of control group and 6.250 nmol/L TP group were (2.07 ± 1.91)%, (9.77 ± 3.52)%, respectively (P<0.05); When the TP concentration increased, DAPK-1mRNA expression increased (P<0.01), DNMT1, DNMT3B mRNA expression significantly dampened (P<0.01); the promoter of LINE-1, DAPK-1 genes were hypermethylation state in the control group, after being treated by TP for 48 h, the brightness of LINE-1, DAPK-1 genes'methylation strips weakened, and the non-methylation strips enhanced all in a dose-dependent manner.

CONCLUSIONTP could down-regulate the transcriptional expression of methyltransferase DNMT1/3B genes, indirect action to reduce the degree of DAPK-1, LINE-1 genes mathylation, thus promote DAPK-1 gene expression level and inhibit the HL 60 cell growth.

DNA (Cytosine-5-)-Methyltransferases ; DNA Methylation ; drug effects ; Death-Associated Protein Kinases ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; HL-60 Cells ; Humans ; Phenanthrenes ; pharmacology ; Promoter Regions, Genetic ; RNA, Messenger