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1.
Article in Chinese | WPRIM | ID: wpr-878861

ABSTRACT

To prepare and optimize the self-microemulsion co-loaded with tenuifolin and β-asarone(TF/ASA-SMEDDS) and evaluate its quality. The prescription compositions of TF/ASA-SMEDDS were screened by solubility test, single factor test and pseudo-tern-ary phase diagram, and the prescriptions were further optimized by Box-Behnken response surface method, with the drug loading and particle size as the evaluation indexes. Then the optimized TF/ASA-SMEDDS was evaluated for emulsified appearance, particle size, morphology and drug release in vitro. The optimized prescription for TF/ASA-SMEDDS was as follows: caprylic citrate triglyceride polyoxyethylene castor oil-glycerol(10.8∶39.2∶50), drug loading of(5.563±0.065) mg·g~(-1) for tenuifolin and(5.526±0.022) mg·g~(-1) for β-asarone; uniform and transparent pan-blue nanoemulsion can be formed after emulsification, with particle size of(28.84±0.44) nm. TEM showed that TF/ASA-SMEDDS can form spherical droplets with a uniform particle size after emulsification; In vitro release test results showed that the drug release rate and cumulative release of tenuifolin and β-asarone were significantly improved. The preparation process of TF/ASA-SMEDDS was simple and can effectively improve in vitro release of tenuifolin and β-asarone.


Subject(s)
Anisoles , Biological Availability , Diterpenes, Kaurane , Drug Delivery Systems , Emulsions , Particle Size , Solubility , Surface-Active Agents
2.
Journal of Experimental Hematology ; (6): 1083-1087, 2019.
Article in Chinese | WPRIM | ID: wpr-775760

ABSTRACT

OBJECTIVE@#To investigate the differentiation of acute promyelocytic leukemia (APL) cells induced by adenosine targeting Prx III.@*METHODS@#HL-60 cells were divided into four groups: control group, all-trans retinoic acid (ATRA) group, adenanthin group and ATRA+adenanthin group. Cell morphologic changes were observed under optical microscope. The influence of adenanthin on the differentiation of HL-60 was observed by nitro blue tetrazolium chloride (NBT) test. Cell surface differentiation antigens CD11b expression was measured by flow cytometry. The protein expression of Prx III was detected by immunohistochemical assay.@*RESULTS@#Adenanthin could induce the differentiation of HL-60 cells; the NBT reduction positive rate in ATRA+adenanthin group was significantly higher than that in ATRA group and adenanthin group (P<0.05). The percentage of CD11b positive cells in ATRA+adenanthin group (43.62%±1.38%) was higher than that in adenanthin group (28.15%±1.78%), ATRA group (36.72%±1.33%) and control group (7.99%±1.78%) (P<0. 05). The content of Prx Ⅲ protein in adenanthin group was significantly higher than that in control group and ATRA group (P<0.05).@*CONCLUSION@#Adenanthin and ATRA have a synergistic effect on the differentiation and maturation of HL-60 cells, and its mechanism may be related with regulation of Prx III expression.


Subject(s)
Cell Differentiation , Diterpenes, Kaurane , HL-60 Cells , Humans , Leukemia, Promyelocytic, Acute , Peroxiredoxin III , Tretinoin
3.
Journal of Experimental Hematology ; (6): 1374-1379, 2019.
Article in Chinese | WPRIM | ID: wpr-775711

ABSTRACT

OBJECTIVE@#To investigate the influence of oridonin on the killing activity of NK-92 MI cells targeting THP1 and the related mechanism.@*METHODS@#The killing activity of NK-92 MI to THP1 before and after oridonin treatment was detected by LDH release assay; the expression of natural killer cell ligands activating receptor D (NKG2D, including MICA, MICB, ULBP1, ULBP2 and ULBP3) was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot respectively; the expression of cytokine TNF-α, TNF-β and IFN-γ in the co-culture supernatant of NK-92 MI cells and THP1 cells were measured by ELISA.@*RESULTS@#The killing efficiency after oridonin treatment at different effector-target ratio (1:1, 5:1, 10:1) was all significantly up-regulated in comparison with that before oridonin treatment (P<0.05). QRT-PCR and Western blot showed that the expressions of mRNA and protein levels of MICB, ULBP1, ULBP2 increased to varying degree (P<0.05), but the expression levels of MICA and ULBP3 were not statistically significant between experimental group and control group (P>0.05). ELISA results indicated that IFN-γ and TNF-β release were significantly increased after oridonin treatment (P<0.05), however, the TNF-α release was not statistically different in comparison with control group (P>0.05).@*CONCLUSION@#Oridonin can significantly improve killing efficiency of NK-92 MI on THP1, that might be related with up-regulation of MICB, ULBP1 and ULBP2 expression and promotion of IFN-γ and TNF-β release.


Subject(s)
Cell Line, Tumor , Diterpenes, Kaurane , Pharmacology , GPI-Linked Proteins , Histocompatibility Antigens Class I , Humans
4.
Article in Chinese | WPRIM | ID: wpr-774293

ABSTRACT

OBJECTIVE@#To investigate the effects of oridonin (ORI) on the proliferation and apoptosis of human multiple myeloma cell line H929 and its possible mechanism.@*METHODS@#H929 cells were exposed to ORI 0、4、8、12、16、20、24、28、32 μmol/L for 12, 24 and 36 hours respectively. The prolifcration inhibitory effect of ORI on H929 cells was determined by MTT assay and then the working concentrations of ORI were determined. The morphological changes and apoptosis of H929 cells were observed by TUNEL (TdT-mediated dUTP Nick-End Labeling) and fluorescence microscopy. The apoptosis rate of H929 cells was detected by flow cytometry with Annexin V-FITC/PI staining. The protein expressions of pro-caspase-3, BCL-2,p-PI3K, p-Akt, BAX, Cleaved PARP and p-JNK, p-ERK and p-p38 in H929 cells were detected by Western blot.@*RESULTS@#Compared with the control group, the proliferation of H929 cells treated with the ORI of 8-16 μmol/L was significantly inhibited and the apoptosis of H929 cells was obviously increased in dose- and time-dependent manners. As for morphological changes, the characteristics of apoptotic cells were presented in H929 cells treated with ORI for 24 hours. The protein levels of pro-caspase-3, BCL-2,p-PI3K, p-Akt were down-regulated with increasing of ORI concentration(r=0.9861, r=0.9725, r=0.9413, r=0.9373), while the BAX, Cleaved PARP and p-JNK, p-ERK and p-p38 were up-regulated(r=0.9178, r=0.8877, r=0.882, r=0.9645, r=0.8623).@*CONCLUSION@#The ORI possesses anti-myeloma effects, can inhibit the proliferation and induce the apoptosis of H929 cell line in vitro. Its potential mechanism may be related with up-regulating the MAPK and down-regulating the PI3K/Akt signal pathways.


Subject(s)
Apoptosis , Caspase 3 , Cell Line, Tumor , Cell Proliferation , Diterpenes, Kaurane , Humans , Multiple Myeloma , Phosphatidylinositol 3-Kinases
5.
Article in English | WPRIM | ID: wpr-773596

ABSTRACT

Nine new ent-kaurane diterpenoids, named scopariusols L-T (1-9), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HR-ESI-MS data, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compound 1 was active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with an IC value of 0.6 μmol·L.


Subject(s)
Animals , Antineoplastic Agents, Phytogenic , Chemistry , Pharmacology , Cell Line, Tumor , Crystallography, X-Ray , Diterpenes, Kaurane , Chemistry , Pharmacology , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal , Chemistry , Pharmacology , HL-60 Cells , Humans , Isodon , Chemistry , Lipopolysaccharides , Pharmacology , Macrophages , Mice , Molecular Structure , Nitric Oxide , Nuclear Magnetic Resonance, Biomolecular , Plant Components, Aerial , Chemistry
6.
Article in English | WPRIM | ID: wpr-812385

ABSTRACT

Nine new ent-kaurane diterpenoids, named scopariusols L-T (1-9), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HR-ESI-MS data, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compound 1 was active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with an IC value of 0.6 μmol·L.


Subject(s)
Animals , Antineoplastic Agents, Phytogenic , Chemistry , Pharmacology , Cell Line, Tumor , Crystallography, X-Ray , Diterpenes, Kaurane , Chemistry , Pharmacology , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal , Chemistry , Pharmacology , HL-60 Cells , Humans , Isodon , Chemistry , Lipopolysaccharides , Pharmacology , Macrophages , Mice , Molecular Structure , Nitric Oxide , Nuclear Magnetic Resonance, Biomolecular , Plant Components, Aerial , Chemistry
7.
Braz. j. med. biol. res ; 51(12): e7599, 2018. graf
Article in English | LILACS | ID: biblio-974261

ABSTRACT

The tumor suppressive role of oridonin, an active compound extracted from Rabdosia rubescens, has been proven in several gastric cancer (GC) cell lines. The present study aimed to evaluate the effect of oridonin on another GC cell line, SNU-216, and explore the potential mechanisms. The viable cell numbers, cell migration, survival fraction, and cell viability were, respectively, evaluated by trypan blue exclusion assay, wound healing assay, clonogenic assay, and CCK-8 assay. Cell apoptosis was determined by flow cytometry assay and western blot. The expression of p53 was inhibited by transient transfection, and the efficiency was verified by western blot. qRT-PCR was performed to measure the mRNA expression of p53. Western blot was used to evaluate the protein expression of apoptosis, DNA damage and p53 function related factors. We found that oridonin significantly inhibited cell proliferation, migration, and survivability, and enhanced cell apoptosis in SNU-216 cells. However, it had no influence on HEK293 cell viability. Oridonin also remarkably enhanced the anti-tumor effect of cisplatin on SNU-216 cells, as it significantly increased apoptotic cells and decreased cell viability. Moreover, the mRNA and protein expression of p53 was significantly up-regulated in oridonin-treated cells, while Mdm2 expression was down-regulated. Furthermore, oridonin enhanced p53 function and induced DNA damage. Knockdown of p53 or employing the caspase inhibitor, Boc-D-FMK, reversed the effect of oridonin on cell viability and apoptosis-related protein expression. The present study demonstrated that oridonin exhibited an anti-tumor effect on GC SNU-216 cells through regulating p53 expression and function.


Subject(s)
Humans , Stomach Neoplasms/pathology , Carcinoma/pathology , Tumor Suppressor Protein p53/analysis , Diterpenes, Kaurane/pharmacology , Antineoplastic Agents/pharmacology , Stomach Neoplasms/metabolism , Stomach Neoplasms/drug therapy , DNA Damage/drug effects , Carcinoma/metabolism , Carcinoma/drug therapy , Cell Survival/drug effects , Blotting, Western , Reproducibility of Results , Apoptosis/drug effects , Reverse Transcriptase Polymerase Chain Reaction , Cell Line, Tumor , Cell Proliferation/drug effects , Caspase 3/analysis , Caspase 9/analysis , HEK293 Cells , Flow Cytometry
8.
Article in Chinese | WPRIM | ID: wpr-300420

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of oridonin on the human acute lymphocytic leukemia cell line Jurkat and its mechanism.</p><p><b>METHODS</b>Jurkat cells were cultured in vitro and treated with various concentrations (0, 1.25, 2.5, 5, and 10 μmol/L) of oridonin for different lengths of time (24, 48, and 72 hours). The proliferation of Jurkat cells was analyzed by MTT assay. The changes in nuclear morphology were evaluated by fluorescence microscopy at 12 hours after treatment with various concentrations of oridonin. The expression levels of Brg1, P53, and C-myc were determined by semi-quantitative Western blot in Jurkat cells treated with various concentrations of oridonin for 24 hours or 5 μmol/L oridonin for various lengths of time (0, 2, 6, 12, and 24 hours). The expression levels of P53 and C-myc and proliferation of Jurkat cells were evaluated after Brg1 expression was knocked down by Brg1-specific siRNA.</p><p><b>RESULTS</b>Compared with the control group, the proliferation of oridonin-treated Jurkat cells was significantly inhibited in a concentration- and time-dependent manner (P<0.05). According to the florescence microscopic analysis, oridonin treatment led to nuclear pyknosis in Jurkat cells. Compared with the control group, Jurkat cells treated with 5 μmol/L oridonin had reduced expression of Brg1 and C-myc but elevated expression of P53. Brg1 knock-down led to a significant reduction in proliferation of Jurkat cells (P<0.05), up-regulated expression of P53, and down-regulated expression of C-myc.</p><p><b>CONCLUSIONS</b>Oridonin can inhibit the proliferation of Jurkat cells, probably via the Brg1 signaling pathway.</p>


Subject(s)
Antineoplastic Agents, Phytogenic , Pharmacology , Cell Proliferation , DNA Helicases , Physiology , Diterpenes, Kaurane , Pharmacology , Dose-Response Relationship, Drug , Down-Regulation , Humans , Jurkat Cells , Nuclear Proteins , Physiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Drug Therapy , Proto-Oncogene Proteins c-myc , Signal Transduction , Physiology , Transcription Factors , Physiology , Tumor Suppressor Protein p53
9.
Chinese Journal of Oncology ; (12): 11-17, 2015.
Article in Chinese | WPRIM | ID: wpr-248417

ABSTRACT

<p><b>OBJECTIVE</b>The aim of this study was to explore the molecular mechanism of apoptosis in esophageal cancer cells induced by Isodon rubescens.</p><p><b>METHODS</b>The DNA-damage effect of Jaridonin was detected by single cell gel electrophoresis (SCGE). The p53 protein was determined by Western blot. GSH assay kit was employed to determine the GSH content in human esophageal cancer EC-1 cells. Intracellular levels of hydrogen peroxide (H2O2) or superoxide (O(2).-) were determined using the redox-sensitive probes 2', 7'-dichlorodihydrofluorescein diacetate (DCF) or dihydroethidium (DHE), and the fluorescence signal was assayed by fluorescence microscopy and by flow cytometry.</p><p><b>RESULTS</b>Jaridonin induced DNA damage in EC-1 cells remarkably. The olive tail moments (OTM) of control and 20, 40 µmol/L Jaridonin were 3.2, 45.2 and 89.0, respectively. Compared with the control, the differences were significant (P < 0.01 for both). Jaridonin resulted in extensive p53 up-regulation in the EC-1 cells. More importantly, the p53 up-regulation occurred as early as 2 h after Jaridonin incubation, and in a time-dependent manner (P < 0.05). p53 siRNA transfection inhibited apoptosis in the EC-1 cells, and the Jaridonin-induced apoptosis rate was reduced from 38.5% to 8.8%. Intracellular level of H2O2 was increased by Jaridonin, whereas the level of O(2).- was barely changed. The GSH content in EC-1 cells was reduced from (10.3 ± 1.6) nmol/mg protein to (4.6 ± 2.1) nmol/mg protein after 20 µmol/L Jaridonin incubation for 8 h, and it was further reduced with the increase of Jaridonin concentration. Jaridonin induced DNA damage, H2O2 accumulation and apoptosis were significantly attenuated in the presence of GSH, but Jaridonin showed little effect on normal human liver L-02 cells.</p><p><b>CONCLUSIONS</b>Jaridonin selectively induces apoptosis in esophageal cancer EC-1 cells through H2O2-mediated DNA damage by depleting GSH.</p>


Subject(s)
Antineoplastic Agents , Pharmacology , Apoptosis , DNA Damage , Diterpenes, Kaurane , Pharmacology , Esophageal Neoplasms , Metabolism , Humans , Hydrogen Peroxide , Metabolism , Up-Regulation
10.
Article in English | WPRIM | ID: wpr-812531

ABSTRACT

The present study was designed to determine the chemical constituents of EtOAc extracts of the aerial parts of Isodon wikstroemioides. Compounds 1-8 were isolated and purified by normal-phase silica gel and reversed-phase C18silica gel column chromatography and HPLC. Their structures were elucidated by extensive spectroscopic methods. Most of them were evaluated for their in vitro cytotoxicity against human cancer HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cells and their inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. Among the eight 11, 20-epoxy-ent-kauranoids isolated, compounds 1-6 (isowikstroemins H-M) were new diterpenoids. Compounds 1, 3, and 7 exhibited significant cytotoxicity with IC50 values ranging from (0.84 ± 0.02) to (4.09 ± 0.34) μmol · L(-1), while compounds 4 and 5 showed selective cytotoxicity. In addition, compounds 1, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages. These results provide a basis for future development of these compounds as anti-cancer and anti-inflammatory agents.


Subject(s)
Anti-Inflammatory Agents , Antineoplastic Agents, Phytogenic , Cell Line, Tumor , Diterpenes, Kaurane , Humans , Inhibitory Concentration 50 , Isodon , Chemistry , Lipopolysaccharides , Pharmacology , Macrophages , Metabolism , Neoplasms , Drug Therapy , Nitric Oxide , Phytotherapy , Plant Components, Aerial , Plant Extracts
11.
Caracas; s.n; ene. 2014. 168 p. ilus, graf. (Ift4872014610197).
Thesis in Spanish | LILACS, LIVECS | ID: biblio-1179273

ABSTRACT

En Venezuela y el mundo, el cáncer es la segunda causa de morbi-mortalidad, y la leucemia es uno de los tipos de cáncer que afecta a nuestra población. La principal características de las celulas linfoides y mieloides presentes en la leucemia es que son pocos funcionales y además no responden a las señales proapoptóticas. Por lo tanto, en la búsqueda de compuestos de mejor perfil terapéutico, se evaluó el efecto de compuestos de tipo seco ent-kauranos aislados de plantas terrestres en las lineas celulares jurka E6.1 y HL60 sobre el crecimiento celular a través del método colorimétrico del MTT, la inducción de apoptosis a través del uso de la microscopia confocal, la citometría de flujo y los micro arreglos de proteínas; y sobre el ciclo celular, la actividad de la vía del NFkB y la diferenciación celular también a través de la citometría de flujo. Se determino que el ácido de casacasina, y la caracasina, disminuyeron la proliferación cecular, indujeron el arresto del ciclo celular, provocaron la externalización de la fosfatidilserina y la activación de las capasas 3, 7, 8 y 9, a la vez que promovieron la disminución del potencial mitocondrial, incrementaron la expresión de las proteínas proapoptóticas en ambas líneas celulares, disminuyeron la activación de la vía de señalización del NFkB en la línea celular Jurkat E6.1, y ademas indujeron la expresión de la proteína CD40 e incrementaron la producción de especies reactivas de oxigeno en la línea celular HL60, por lo que estos compuestos ent-kauranos poseen un alto potencial anticancerígeno para la leucemia linfocítica aguda de células T y para la leucemia promielocítica


Subject(s)
Humans , Leukemia, Promyelocytic, Acute/metabolism , Apoptosis/drug effects , Diterpenes, Kaurane/pharmacology , Cell Proliferation/drug effects , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Phosphatidylserines/metabolism , Leukemia, Promyelocytic, Acute/pathology , Leukemia, Promyelocytic, Acute/prevention & control , Leukemia, T-Cell/pathology , Leukemia, T-Cell/prevention & control , Cell Differentiation , Reactive Oxygen Species , Jurkat Cells , Diterpenes, Kaurane/metabolism , Diterpenes, Kaurane/therapeutic use , Apoptosis Regulatory Proteins/drug effects , Apoptosis Regulatory Proteins/metabolism
12.
Article in Chinese | WPRIM | ID: wpr-349707

ABSTRACT

This study was purposed to investigate the antitumor effect of oridonin on human multiple myeloma cell line U266 and its possible mechanism. The CCK-8 test was used to determine the inhibitory effect of oridonin on proliferation of U266 cells. The morphological changes of U266 cells were observed under optical microscope. The apoptosis rate of U266 cells was detected by flow cytometry. The mRNA levels of FGFR3, BCL2, CCND1 and MYC genes were quantified by using real-time quantitative PCR method, and the protein levels of BCL2, MYC, CCND1, FGFR3 and P53 were detected by Western blot. The results showed that the oridonin obviously inhibited the growth of U266 cell in dose-and time-dependent manners. As for morphological changes, characteristic apoptotic cells presented in U266 cells treated with 10 µmol/L oridonin for 24 hours. The apoptotic rate of U266 cells increased in dose and time dependent manners; after treatment of U266 cells with oridonin the mRNA levels of FGFR3, BCL2, CCND1 and MYC as well as the their protein levels decreased. Occasionally, the oridonin up-regulated the protein levels of P53 in the same manner. It is concluded that the oridonin can exert its anti-tumor effect by inhibiting proliferation and inducing apoptosis of U266 cell in dose dependent and time dependent manners, that maybe give the clues about new program of target therapy for multiple myeloma.


Subject(s)
Antineoplastic Agents , Pharmacology , Apoptosis , Cell Line, Tumor , Cell Proliferation , Diterpenes, Kaurane , Pharmacology , Humans , Multiple Myeloma , Pathology
13.
Article in Chinese | WPRIM | ID: wpr-251742

ABSTRACT

<p><b>OBJECTIVE</b>To prepare freeze-dried long-circulation oridonin liposomes with optimized parameters.</p><p><b>METHODS</b>Ethanol injection method followed by freeze-drying was used to prepare the liposomes. Sephadex column was used to purify liposomes. Effects of formulation factors on entrapment efficiency of long-circulation oridonin liposomes were studied. The particle size, distribution and in vitro release were determined. Pharmacokinetics of oridonin liposomes in rats was determined by HPLC and the pharmacokinetic parameters calculated by Kinetica(TM) software were compared with conventional oridonin liposomes and solution.</p><p><b>RESULTS</b>The optimized lipid formulation for long-circulation liposomes was composed of soy lecithin, cholesterol and DSPE-PEG 2000 with a ratio of 1:0.5:1.8(w/w). The ratio of drug to lipid was 1:6. Freeze-drying protectant was a mixture of glucose and mannitol (3:1). The entrapment efficiency (EE) of long-circulation oridonin liposomes was about 65%. The particle size of liposomes after hydrolyzation was 164 nm with good DPI. The liposomes showed a sustained drug release in vitro. Intravenous injected oridonin fitted with two-compartment pharmacokinetic model. The MRT of long-circulation liposomes was 2 times and 6 times and AUC was about 2 times and 3 times of conventional liposomes and oridonin solution, respectively.</p><p><b>CONCLUSION</b>Freeze-dried liposomes with high EE have been obtained by the proposed approach. This long-circulation liposomes extend oridonin half time and significantly increase AUC in rats.</p>


Subject(s)
Animals , Delayed-Action Preparations , Diterpenes, Kaurane , Pharmacokinetics , Drug Stability , Freeze Drying , Liposomes , Pharmacokinetics , Male , Rats , Rats, Sprague-Dawley , Tissue Distribution
14.
Article in English | WPRIM | ID: wpr-293273

ABSTRACT

Oridonin, a diterpenoid isolated from Rabdosia rubescens, has been proven to possess various pharmacological and physiological effects such as anti-inflammation, anti-bacterial, and anti-neoplastic, although in recent years, more attention has been paid to its anti-neoplastic effects. For example, oridonin can trigger cell cycle arrest, apoptosis, and autophagy in different neoplastic cell lines. This review summarizes the considerable knowledge about the action mechanisms of oridonin that has been studied in recent years. The present observations reveal the novel anti-neoplastic effects of oridonin, suggesting that it may be effective as a potent alternative or adjunct drug to conventional chemotherapy.


Subject(s)
Animals , Antineoplastic Agents , Chemistry , Pharmacology , Therapeutic Uses , Apoptosis , Cell Cycle , Diterpenes, Kaurane , Chemistry , Pharmacology , Therapeutic Uses , Humans , Neoplasms , Drug Therapy , Pathology , Signal Transduction
15.
Journal of Breast Cancer ; : 133-137, 2013.
Article in English | WPRIM | ID: wpr-59655

ABSTRACT

Curcumin, which is extracted from the plant Curcuma longa, has been used in the therapeutic arsenal for clinical oncology. Curcumin has chemopreventive and antitumoral activities against some aggressive and recurrent cancers. The expressions and activities of various proteins, such as inflammatory cytokines and enzymes, transcription factors, and gene-products linked with cell survivals and proliferation, can be modified by curcumin. Moreover, curcumin decreases the toxic effect of mitomycin C. Though curcumin has shown highly cytotoxic to some cancer cell lines, curcumin is insoluble and instable in water. The solubility of curcumin could be enhanced by utilizing the solubilizing properties of rubusoside. In addition, the selective delivery of synthetic analogs or nanotechnology-based formulations of curcumin to tumors may improve the chemopreventive and chemotherapeutic effects. The focus of this short review is to describe how curcumin participates in antitumor processes in breast cancer cells.


Subject(s)
Breast , Breast Neoplasms , Cell Line , Curcuma , Curcumin , Cytokines , Diterpenes, Kaurane , Glucosides , Imidazoles , Medical Oncology , Mitomycin , Molecular Mechanisms of Pharmacological Action , Niacin , Plants , Proteins , Solubility , Transcription Factors , Water
16.
Article in Chinese | WPRIM | ID: wpr-315028

ABSTRACT

An HPLC method was developed for simultaneous quantitation of rosmarinic acid, oridonin and chrysoplenetin in the aerial parts of Isodon rubescens. Samples were analyzed on an Ultimate C18 column (4.6 mm x 250 mm, 5 microm) with methanol and water containing 0.1% formic acid as mobile phases in a linear gradient mode. The flow rate was 1.0 mL x min(-1) and the temperature was set at 30 degrees C. The PDA detector wavelengths were set at 338 nm for rosmarinic and chrysoplenetin and at 242 nm for oridonin. The linear ranges were 0.222-2.78, 0.227-2.84 and 0.005-0.071 microg for rosmarinic acid, oridonin and chrysoplenetin, respectively. The average recoveries of the three constituents were 102.9% (RSD 1.9%), 99.6% (RSD 1.1%) and 102.5% (RSD 0.94%), respectively. This method was proved to be accurate and repeatable, and can be used for quality control of the aerial parts of I. rubescens.


Subject(s)
Chromatography, High Pressure Liquid , Methods , Cinnamates , Depsides , Diterpenes, Kaurane , Drugs, Chinese Herbal , Flavonoids , Isodon , Chemistry , Plant Extracts , Plants, Medicinal , Chemistry
17.
Article in English | WPRIM | ID: wpr-812690

ABSTRACT

AIM@#To discover more active and water-soluble derivatives of tetracyclic diterpenoids containing an exo-methylene cyclopentanone or an α-methylenelactone moiety.@*METHODS@#All of the key intermediates were synthesized from stevioside, and the target compounds were obtained through glycosylation of the 4-carboxyl group. The cytotoxicity of the target compounds against six human cancer cell lines, HepG2, Bel-7402, A549, U251, MCF-7 and MDA-MB-231, were evaluated by the MTT assay.@*RESULTS@#Compound 1b was more effective than the positive control adriamycin against the HepG2, Bel-7402, A549, MCF-7, and MDA-MB-231 cell lines with IC50 values of 0.12, 0.91, 0.35, 0.08, and 0.07 μmol·L(-1), respectively. Moreover, compound 3c exhibited the most potent and selective cytotoxic activity against the HepG2 cell line (IC50, 0.01 μmol·L(-1)).@*CONCLUSION@#Compounds 1b and 3c could be considered as potential anticancer candidates for further study.


Subject(s)
Antineoplastic Agents , Chemistry , Toxicity , Cell Line, Tumor , Cell Proliferation , Diterpenes, Kaurane , Chemistry , Toxicity , Drug Evaluation, Preclinical , Glycosylation , Humans , Molecular Structure
18.
Article in Chinese | WPRIM | ID: wpr-263339

ABSTRACT

The aim of this study was to investigate the biological effect of longikaurin A on multiple myeloma H929 cells. Effects of oridonin and longikaurin A on proliferation of H929 cells were evaluated by CCK-8 assay. Cell morphological features of H929 cells were examined under inverted phase contrast microscope. Apoptosis was determined by Annexin V/PI staining. Expression of caspase-3, caspase-9, and PARP were detected by Western blot. Reactive oxygen species (ROS) level was determined by DCFDA assay. The results showed that longikaurin A (IC(50) 0.85 µmol/L) was more effective than oridonin ((IC(50) 10.66 µmol/L) to inhibit the proliferation of H929 cells. Treatment with longikaurin 2 µmol/L significantly increased the percentage of Annexin V positive cells. Caspase-3 and caspase-9 were activated and PARP, one substrate of caspase-3, was cleaved into 85 kDa fragments. The ROS scavenger N-acetyl-cysteine significantly blocked apoptosis induced by longikaurin A. However, longikaurin A did not increase the ROS level in H929 cells. It is concluded that longikaurin A is more effective than oridonin to induce apoptosis in multiple myeloma H929 cells without increasing the ROS level.


Subject(s)
Apoptosis , Caspase 3 , Metabolism , Caspase 9 , Metabolism , Cell Line, Tumor , Diterpenes, Kaurane , Pharmacology , Humans , Multiple Myeloma , Pathology , Reactive Oxygen Species , Metabolism
19.
Article in Chinese | WPRIM | ID: wpr-355615

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effects of oridonin (Ori) on human multiple myeloma (MM) cell line LP-1 apoptosis and its mechanisms.</p><p><b>METHODS</b>The human MM LP-1 cells were incubated in vitro by different concentrations of Ori. The proliferation activities of LP-1 cells were detected using MTT assay. The apoptosis rate of LP-1 cells was detected using Annexin V/PI double staining method. The ultrastructural changes of LP-1 cells were observed under transmission electron microscope (TEM) after they were treated with Ori. The mRNA expression of apoptosis correlated genes were detected using Real-time PCR.</p><p><b>RESULTS</b>Ori inhibited the proliferation of LP-1 cells in a dose- and time-dependent way. Results of Annexin V/PI double staining method showed that, along with increased drug concentration and prolonged drug action time, the apoptosis rate of LP-1 cells significantly increased. Under TEM, chromatin margination and mitochondrial swelling could be seen in LP-1 cells after they were treated by Ori. The mRNA expressions of PDCD5 and Bid were up-regulated, and those of Bcl-2 and NK-kappaB were down-regulated after action of Ori.</p><p><b>CONCLUSIONS</b>Ori induced cell apoptosis by up-regulating the mRNA expression of Bid and down-regulating the mRNA expression of Bcl-2 to decrease the mitochondrial membrane potential, trigger mitochondrial apoptosis way of LP-1 cells. Ori, also as the inhibitor of NF-kappaB activities, blocked the NF-kappaB activation, induced cell apoptosis, and inhibited the cell proliferation. Of them, it is necessary to further study the role of PDCD5 as an apoptosis promoter.</p>


Subject(s)
Apoptosis , Apoptosis Regulatory Proteins , Metabolism , BH3 Interacting Domain Death Agonist Protein , Metabolism , Cell Line, Tumor , Cell Proliferation , Diterpenes, Kaurane , Pharmacology , Humans , Multiple Myeloma , Pathology , NF-kappa B p50 Subunit , Metabolism , Neoplasm Proteins , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism
20.
Chinese Journal of Hematology ; (12): 439-443, 2012.
Article in Chinese | WPRIM | ID: wpr-359463

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the anti-leukemia effect of oridonin on Ph(+) acute lymphoblastic leukemia (ALL) cell line SUP-B15.</p><p><b>METHODS</b>Human Ph(+) ALL cell line was cultured in vitro. The 50% inhibition concentration (IC(50)) of oridonin against SUP-B15 cell line was examined using modified MTT assay. The cellular morphologic changes were observed using a light microscope. The percent of apoptosis of SUP-B15 cell line after drug treatment was evaluated by flow cytometric analysis. The active levels of ABL kinase and its downstream Akt/mTOR, Raf/MEK/ERK, STAT5 signaling pathways and the expression levels of Bcl-2 and BAX were examined by Western blot.</p><p><b>RESULTS</b>Oridonin inhibited the growth of SUP-B15 cell line in both time- and dose-dependent manner with the IC(50) of oridonin as (7.08 ± 1.21) µmol/L after 72 h treatment. The cellular membrane of SUP-B15 cell line treated with oridonin became unsharp, some of them disintegrated. Oridonin induced apoptosis in SUP-B15 cell line with the apoptosis rates following 0, 5, 10 µmol/L oridonin treatment for 24 h were (6.67 ± 0.83)%, (18.30 ± 1.79)% and (37.63 ± 7.12)%, respectively. Oridonin inhibited activation of ABL kinase and its downstream Akt/mTOR, Raf/MEK/ERK and STAT5 signaling pathways, which were constitutively activated in SUP-B15 cell line, down-regulated the level of anti- apoptotic protein Bcl-2 and up-regulated the expression of pro-apoptotic protein Bax.</p><p><b>CONCLUSION</b>Oridonin exerted anti-leukemia effect in Ph(+)ALL cell line SUP-B15 by inhibiting the activation of ABL kinase and its downstream Akt/mTOR, Raf/MEK/ERK and STAT5 signaling pathways, down-regulating the expression of Bcl-2 and up-regulating the expression of BAX.</p>


Subject(s)
Apoptosis , Cell Line, Tumor , Cell Proliferation , Diterpenes, Kaurane , Pharmacology , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Metabolism , Pathology , Signal Transduction
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