OBJECTIVEUnder various drought conditions and nitrogen application, the content of vindoline, catharanthine, vincristine and vinblastine in the leaf of Catharanthus roseus were illustrated to improve the content of alkaloid theoretically.

METHODSix groups were set in the experiment, which included: CK (natural control), CN (natural control + nitrogen), LK (low drought), LN (low drought + nitrogen), HK (high drought), HN (high drought + nitrogen) to discuss the change characteristics of total nitrogen, the activity of alkaline POD and TDC, the content of four alkaloids under the different conditions were measured.

RESULTUnder LK condition, the activity of POD, TDC were enhanced. In the early stage of stress (0-21 d), vindoline, catharanthine, vincristine and vinblastine accumulated, and reduced in the later stage (28-35 d). For all groups, adding exogenous nitrogen could improve the total content of nitrogen, vindoline and vinblastine, meanwhile the activity of POD and TDC were enhanced as well. The LN, HN treatments were beneficial to accumulating catharanthine and vinblastine.

CONCLUSIONDrought stress or additional nitrogen have an influence on both of the activities of POD and TDC, and the four alkaloids were affected as well. Thereinto, the LN condition was the most effective treatment for accumulating the four alkaloids (vindoline, catharanthine, vincristine and vinblastine), which were regulated by improve nitrogen content and enzymatic activity.

Catharanthus ; metabolism ; Nitrogen ; metabolism ; Peroxidase ; metabolism ; Stress, Physiological ; Vinblastine ; analogs & derivatives ; metabolism ; Vinca Alkaloids ; metabolism ; Vincristine ; metabolism ; Water ; metabolism

In this paper, the fluorogenic property of vindoline was exploited and, as a probe, used to analyze the interaction of vindoline with HSA by fluorescence and absorption spectra in combination with molecular modeling under a simulated physiological conditions. The evidences from synchronous fluorescence and absorption spectroscopes showed the effect of vindoline on the microenvironment around HSA in aqueous solution. Data obtained by the fluorescence spectroscopy indicated that binding of vindoline with HSA leads to dramatic enhancement of the fluorescence emission intensity. The binding constants and the number of binding sites between vindoline and HSA at different temperatures (303, 310 and 317 K) were calculated according to the data obtained from fluorescence titration. Molecular docking was performed to reveal the possible binding mode or mechanism and suggested that vindoline can bind strongly to HSA. It is considered that vindoline binds to HSA mainly by a hydrophobic interaction and there are four hydrogen bonds interactions between the drug and the residues Ala291, Arg222, Arg218 and Lys195, separately. Fluorescent displacement measurements confirmed that vindoline bind HSA on site II. The thermodynamic parameters obtained (the enthalpy change deltaH0 and the entropy change deltaS0 were calculated to be -10.30 kJ x mol(-1) and 79.98 J x mol(-1) x K(-1), respectively, according to the Van't Hoff equation) suggested that hydrophobic and electrostatic interaction is the predominant intermolecular forces stabilizing the complex.
Antineoplastic Agents, Phytogenic ; metabolism ; Binding Sites ; Computer Simulation ; Humans ; Protein Binding ; Serum Albumin ; chemistry ; metabolism ; Spectrometry, Fluorescence ; Spectrophotometry, Ultraviolet ; Thermodynamics ; Vinblastine ; analogs & derivatives ; metabolism

Aged ; Antineoplastic Agents, Phytogenic ; adverse effects ; Extravasation of Diagnostic and Therapeutic Materials ; therapy ; Humans ; Male ; Negative-Pressure Wound Therapy ; methods ; Vinblastine ; adverse effects ; analogs & derivatives

Catharanthus roseus (L.) G. Don is a plant of the Catharanthus genus of Apocynaceae which has been reported to have therapeutic effects of detoxication and anticancer. In order to further study the alkaloid constituents of C. roseus, the aerial parts of the plant were extracted with 95% EtOH, and then treated with 2% H2SO4 and NH3H2O to obtain total alkaloids. The total alkaloids were separated and purified by column chromatography over silica gel and prepared by high performance liquid chromatography (HPLC). Their structures were elucidated on the basis of physicochemical properties and spectral data. A new alkaloid together with five known compounds were isolated and identified as vindolinine B (1), lochnericine (2), horhammericine (3), vindorosine (4), vindoline (5), and coronaridine (6). Compound 1 is a new compound and named as vindolinine B.
Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; Catharanthus ; chemistry ; Ibogaine ; analogs & derivatives ; chemistry ; isolation & purification ; Indole Alkaloids ; chemistry ; isolation & purification ; Molecular Structure ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry ; Vinblastine ; analogs & derivatives ; chemistry ; isolation & purification

This study was purposed to explore the Rituximab (RTX)-mediated sensitization of B-NHL cell lines to apoptosis induced by Gemcitabine or Navelbine and its possible mechanism. The inhibitory rate of B-NHL cell proliferation was detected by XTT method, the IC₅₀ from Gemcitabine or Navelbine and combination of Gemcitabine or Navelbine with RTX was compared. The expression level of antiapoptotic protein BCL-2 in Daudi, Ramos, Raji and Namalwa cells treated with RTX of 20 μg/ml for 24 hours was detected by Western blot. The results showed that the RTX as a single agent could weakly induce the apoptosis of Daudi, Namalwa, Raji and Ramos lymphoma cell lines, the inhibiting rate of cell proliferation ranged from 3% to 10%; RTX could sensitize significantly the cytotoxity of Gemcitabine or Navelbine in Daudi, Namalwa and Raji cell lines; The expression of BCL-2 in Raji and Namalwa cell lines treated with RTX of 20 microg/ml for 24 hours was down-regulated. It is concluded that RTX can sensitize the cytotoxicity of Gemcitabine or Navelbine to the human lymphoma cell lines which displayed the synergistic effect on Daudi, Namalwa and Raji cell lines. The BCL-2 expression level in Raji and Namalwa cell lines treated by RTX is down-regulated which may be one of the mechanisms sensitizing the cytotoxicity of Gemcitabine or Navelbine.
Antibodies, Monoclonal, Murine-Derived ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; drug effects ; Cytotoxicity, Immunologic ; drug effects ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Humans ; Lymphoma, T-Cell ; Proto-Oncogene Proteins c-bcl-2 ; Rituximab ; Vinblastine ; analogs & derivatives ; pharmacology

Anthracyclines ; pharmacology ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Drug Resistance, Neoplasm ; Female ; Humans ; Taxoids ; administration & dosage ; Vinblastine ; administration & dosage ; analogs & derivatives

We think the strategy of classic natural product-based drug discovery will be an effective way for us to develop new drugs with independent intellectual property. The strategy includes: to study the molecular mechanism of action of classic natural product with chemical genetics and chemical biology approaches firstly; then establish the proper in vitro bioassay or bioassay system based on its molecular mechanism for their pharmacodynamic evaluation; finally, study their structure-activity, structure-toxicity and structure-ADME properties with medicinal chemistry.
Animals ; Anti-HIV Agents ; chemical synthesis ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemical synthesis ; pharmacology ; Berberine ; analogs & derivatives ; chemical synthesis ; pharmacology ; Biological Products ; chemical synthesis ; chemistry ; pharmacology ; Camptothecin ; analogs & derivatives ; chemical synthesis ; pharmacology ; Drug Discovery ; Humans ; Hypoglycemic Agents ; chemical synthesis ; pharmacology ; Oleanolic Acid ; analogs & derivatives ; chemical synthesis ; pharmacology ; Triterpenes ; chemical synthesis ; pharmacology ; Vinblastine ; analogs & derivatives ; chemical synthesis ; pharmacology

OBJECTIVETo evaluate the clinical efficacy and toxicity of vinorelbine (N) and epirubicin (E) as the neoadjuvant chemotherapy regimen in the treatment of locally advanced breast cancer (LABC).

METHODSFrom September 2001 to December 2004, 158 patients with LABC were treated with NE chemotherapy before operation. Neoadjuvant chemotherapy containing vinorelbine (N), 25 mg/m(2) (days 1 and 8) and epirubicin (E), 60 mg/m(2) (days 1) was administered every 3 weeks for three cycles before local treatment.

RESULTSResponse in the breast: the clinical objective response was 81.6% [23.4% (37/158) cCR and 58.2% (92/158) PR], 16.5% (26/158) SD and 1.9% (3/158) PD. Pathological complete response was found in 29 cases (18.3%). Eighteen cases (26.5%) who have positive FNA result in the axillary lymphnode before chemotherapy showed negative result in the surgery specimen. The most common toxicities were neutropenia, alopecia and nausea/vomiting. Neutropenia grade 3 - 4 was reported in 111 patients (70.3%) and there was no toxic deaths.

CONCLUSIONSThe combination of vinorelbine and epirubicin is a very active and well-tolerated regimen as neoadjuvant chemotherapy for the LABC.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Chemotherapy, Adjuvant ; Drug Administration Schedule ; Epirubicin ; administration & dosage ; Female ; Humans ; Middle Aged ; Neoplasm Staging ; Treatment Outcome ; Vinblastine ; administration & dosage ; analogs & derivatives

BACKGROUND AND OBJECTIVEHuman telomerase reverse transcriptase is the catalytic subunit of telomerase, and its activity is correlated with cell's sensitivity to chemotherapy. The aim of this study is to investigate the differential expression of human telomerase reverse transcriptase (hTERT) mRNA in human lung adenocarcinoma cell line Anip973 and Anip973/NVB, and to observe the correlation between hTERT mRNA and drug-resistance.

METHODSThe real-time fluorescence quantitative RT-PCR was used to detect the change of hTERT mRNA in human lung adenocarcinoma drug-resistant cell Anip973/NVB and parental cell Anip973 treated by NVB.

RESULTSIn the control group, the expression of hTERT mRNA showed no significant difference between drug-resistant cell Anip973/NVB and parental cell Anip973. After been treated by NVB, the expression of hTERT mRNA in parental cell was significantly decreased (P < 0.01), and drug-resistant cell Anip973/ NVB had no evidently variant (P > 0.05). The down-regulated hTERT mRNA in Anip973 cell was higher than that in Anip973/ NVB cell.

CONCLUSIONTelomerase correlates with the drug-resistant cell A973/NVB, and telomerase may be a new target for multi-drug resistant inversion.

Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; genetics ; physiology ; Humans ; Lung Neoplasms ; genetics ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Telomerase ; genetics ; Vinblastine ; analogs & derivatives ; pharmacology

BACKGROUND AND OBJECTIVECisplatin (DDP) plus vinorelbine (NVB) constitute the first-line regimen (NP regimen) for non-small cell lung cancer (NSCLC). Oxaliplatin (OXA) is another effective drug in treatment of NSCLC with mild toxicities to gastrointestinal tract, kidney and bone marrow. The aim of this study is to evaluate the efficiency and safety between NVB plus OXA (NO) regimen and NP regimen for advanced NSCLC.

METHODSWe searched CBM CNKI, VIP, Cochrane Library, PubMed, EMBASE, ASCO etc. conference proceedings and internet information. Randomized controlled trials of NO versus NP for advanced NSCLC were included; we evaluated the quality of the included studies and analyzed data by Cochrane Collaboration's RevMan 5.0 software.

RESULTSFourteen randomized trials involving 1 270 patients were included. There were no statistical differences between NO and NP in overall response rate, disease control rate, 1-year survival rate, anemia and thrombocytopenia. Gastrointestinal toxicity, leucopenia, alopecia and kidney toxicity were more serious in NP (P < 0.05), but neuritis was more serious in NO, with significant difference (P < 0.05).

CONCLUSIONThe clinical efficacy of NO and NP for advanced NSCLC was similar, but the side effects were different. The toxicity of NO has the tendency to be more tolerable.

Antineoplastic Combined Chemotherapy Protocols ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cisplatin ; adverse effects ; therapeutic use ; Humans ; Lung Neoplasms ; drug therapy ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Vinblastine ; adverse effects ; analogs & derivatives ; therapeutic use