Wogonin is a plant flavonoid compound extracted from Scutellaria baicalensis (Huang-Qin or Chinese skullcap) and has been studied thoroughly by many researchers till date for its anti-viral, anti-oxidant, anti-cancerous and neuro-protective properties. Numerous experiments conducted in vitro and in vivo have demonstrated wogonin's excellent tumor inhibitory properties. The anti-cancer mechanism of wogonin has been ascribed to modulation of various cell signaling pathways, including serine-threonine kinase Akt (also known as protein kinase B) and AMP-activated protein kinase (AMPK) pathways, p53-dependent/independent apoptosis, and inhibition of telomerase activity. Furthermore, wogonin also decreases DNA adduct formation with a carcinogenic compound 2-Aminofluorene and inhibits growth of drug resistant malignant cells and their migration and metastasis, without any side effects. Recently, newly synthesized wogonin derivatives have been developed with impressive anti-tumor activity. This review is the succinct appraisal of the pertinent articles on the mechanisms of anti-tumor properties of wogonin. We also summarize the potential of wogonin and its derivatives used alone or as an adjunct therapy for cancer treatment. Furthermore, pharmacokinetics and side effects of wogonin and its analogues have also been discussed.
Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; DNA Adducts ; metabolism ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Flavanones ; pharmacology ; therapeutic use ; Humans ; Neoplasms ; drug therapy ; metabolism ; Phytotherapy ; Scutellaria baicalensis ; chemistry ; Signal Transduction ; drug effects

EGFR and KRAS mutations are two of the most common mutations that are present in lung cancer. Screening and detecting these mutations are of issue these days, and many different methods and tissue samples are currently used to effectively detect these two mutations. In this study, we aimed to evaluate the testing for EGFR and KRAS mutations by pyrosequencing method, and compared the yield of cytology versus histology specimens in a consecutive series of patients with lung cancer. We retrospectively reviewed EGFR and KRAS mutation results of 399 (patients with EGFR mutation test) and 323 patients (patients with KRAS mutation test) diagnosed with lung cancer in Konkuk University Medical Center from 2008 to 2014. Among them, 60 patients had received both EGFR and KRAS mutation studies. We compared the detection rate of EGFR and KRAS tests in cytology, biopsy, and resection specimens. EGFR and KRAS mutations were detected in 29.8% and 8.7% of total patients, and the positive mutation results of EGFR and KRAS were mutually exclusive. The detection rate of EGFR mutation in cytology was higher than non-cytology (biopsy or resection) materials (cytology: 48.5%, non-cytology: 26.1%), and the detection rate of KRAS mutation in cytology specimens was comparable to non-cytology specimens (cytology: 8.3%, non-cytology: 8.7%). We suggest that cytology specimens are good alternatives that can readily substitute tissue samples for testing both EGFR and KRAS mutations. Moreover, pyrosequencing method is highly sensitive in detecting EGFR and KRAS mutations in lung cancer patients.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/genetics/metabolism/*pathology ; DNA Mutational Analysis ; DNA, Neoplasm/chemistry/metabolism ; Female ; Humans ; Lung Neoplasms/genetics/metabolism/*pathology ; Male ; Middle Aged ; Mutation ; Receptor, Epidermal Growth Factor/*genetics/metabolism ; Retrospective Studies ; ras Proteins/*genetics/metabolism

OBJECTIVETo explore the effect of folate on cell proliferation and apoptosis as well as on DNA methylation, expression of mRNA and protein of fragile histidine triad (FHIT)gene in cervical cancer cells.

METHODSCervical cancer cell lines including CaSki (HPV16-positive) and C33A (HPV-negative)were cultured in vitro with different folate concentrations. Cell proliferation and apoptosis were determined by viable cell counting and flow cytometry while FHIT gene DNA methylation was used with methylation specific PCR (MSP). Both gene expression of FHIT protein and mRNA were detected by Western blot and Real-time PCR, respectively.

RESULTSFolate could inhibit the proliferation and promote the apoptosis in two kinds of cervical cancer cells. The number of viable cells decreased (C33A:r = 0.98, P < 0.001; CaSki:r = 0.98, P < 0.001) and the apoptosis rate increased (C33A:r = 0.98, P < 0.001; CaSki:r = 0.99, P < 0.001) along with the increase of folate concentration. FHIT gene DNA methylation showed all positive at the folate concentration levels of 1 µg/ml and 10 µg/ml, partially positive at 100 µg/ml and 250 µg/ml, but negative at 500 µg/ml and 1 000 µg/ml in both C33A and CaSki cells. Comparing with the control group, the mRNA or protein relative expression levels of FHIT gene in different folate concentrations were statistically significant in two kinds of cells, and showing that the FHIT gene mRNA expression (C33A:r = 0.96, P < 0.001; CaSki:r = 0.94, P < 0.001) and protein expression (C33A:r = 0.96, P < 0.001; CaSki:r = 0.97, P < 0.001) both increased along with the increase of folate concentration.

CONCLUSIONOur findings indicated that adequate folate seemed to be able to effectively inhibit the proliferation of cervical cancer cells and facilitate their apoptosis in vitro, so would reverse the aberration mRNA and protein expression of FHIT gene.

Acid Anhydride Hydrolases ; genetics ; metabolism ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Culture Media ; chemistry ; DNA Methylation ; Female ; Folic Acid ; pharmacology ; Humans ; Neoplasm Proteins ; genetics ; metabolism ; Uterine Cervical Neoplasms ; genetics ; pathology

A series of cycloberberine derivatives were designed, synthesized and evaluated for their anti-cancer activities in vitro. Among these analogs, compounds 6c, 6e and 6g showed strong inhibition on human HepG2 cells. They afforded a potent effect against DOX-resistant MCF-7 breast cells as well. The primary mechanism showed that cell cycle was blocked at G2/M phase of HepG2 cells treated with 6g using flow cytometry assay. It significantly inhibited the activity of DNA Top I at the concentration of 0.1 mg mL-1. Our results provided a basis for the development of this kind of compounds as novel anti-cancer agents.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Berberine ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; DNA Topoisomerases, Type I ; metabolism ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Molecular Structure ; Structure-Activity Relationship

Animals ; Apoptosis ; Cell Cycle ; Cell Cycle Proteins ; genetics ; metabolism ; physiology ; DNA Repair ; Homeodomain Proteins ; genetics ; metabolism ; physiology ; Humans ; Inhibitor of Growth Protein 1 ; Intracellular Signaling Peptides and Proteins ; genetics ; metabolism ; physiology ; Neoplasm Metastasis ; Neoplasms ; metabolism ; pathology ; Neovascularization, Pathologic ; pathology ; Nuclear Proteins ; genetics ; metabolism ; physiology ; Prognosis ; Receptors, Cytoplasmic and Nuclear ; genetics ; metabolism ; physiology ; Signal Transduction ; Transcription Factors ; genetics ; metabolism ; physiology ; Tumor Suppressor Protein p53 ; metabolism ; Tumor Suppressor Proteins ; chemistry ; genetics ; metabolism ; physiology

OBJECTIVE: To analyze the mdr-1 gene promoter methylation and histone acetylation status in both MCF-7/Adr and MCF-7 cells and to preliminarily explore the epigenetic mechanism of multidrug resistance in breast cancer. METHODS: mdr-1 gene promoter methylation status of the 2 cell lines was detected by methylation-sensitive PCR. mRNA expression of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) was detected by real-time quantitative PCR. Acetylation level of histone H3 and H4 was examined by optical density assay. RESULTS: Promoter hypermethylation of mdr-1 gene was observed in MCF-7 cells whereas hypomethylation was found in MCF-7/Adr cells. Expression of DNMT1, DNMT3a, and DNMT3b mRNA in MCF-7/Adr cells significantly decreased compared with that of MCF-7 cells (P<0.05). H3 and H4 histone acetylation levels of MCF-7/Adr cells were obviously higher than those of the MCF-7 cells (P<0.01). Expression of HDAC1, HDAC2, HDAC7, and Sirtuin type 1 (SIRT1) mRNA in MCF-7/Adr cells was significantly reduced (P<0.05). CONCLUSION Hypomethylation of the promoter region of mdr-1 gene, high H3 and H4 histone acetylation, and low mRNA expression of DNMTs and HDACs may be important epigenetic factors for the development of MDR in MCF-7/ Adr cells.
ATP Binding Cassette Transporter, Subfamily B, Member 1 ; genetics ; Acetylation ; Breast Neoplasms ; pathology ; Cell Line, Tumor ; DNA (Cytosine-5-)-Methyltransferase 1 ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; metabolism ; DNA Methylation ; genetics ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Epigenesis, Genetic ; Female ; Histone Deacetylases ; genetics ; metabolism ; Histones ; chemistry ; Humans ; Promoter Regions, Genetic ; genetics ; RNA, Messenger ; genetics ; metabolism

OBJECTIVETo obtain the entire coding sequence of human PRL-3 gene and construct its prokaryotic expression vector.

METHODSWith total RNA extracted from the human colorectal carcinoma cell line SW480 as the template, PRL-3 gene was amplified by RT-PCR with primers designed according to the published sequence of GenBank, and the product was inserted into pGEM-T Easy vector. The recombinant plasmid pGEM-T-PRL-3 was identified by restriction endonuclease analysis and DNA sequencing. After digestion with restriction endonuclease, PRL-3 gene was cloned into the multicloning sites of the prokaryotic expression vector pGEX-4T-1.

RESULTS AND CONCLUSIONThe entire coding region of human PRL-3 gene was cloned, and the recombinant pGEX-4T-1-PRL-3 vector was successfully constructed and expressed, which may provide the basis for further study of the relationship between human colorectal carcinoma and PRL-3 gene.

Base Sequence ; Cell Line, Tumor ; Cloning, Molecular ; DNA, Complementary ; chemistry ; genetics ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli ; genetics ; Genetic Vectors ; genetics ; Humans ; Molecular Sequence Data ; Neoplasm Proteins ; genetics ; metabolism ; Protein Tyrosine Phosphatases ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; Sequence Analysis, DNA

OBJECTIVETo explore the effect of Rg3 on inhibiting and inducing apoptosis of bladder cancer cells.

METHODThe bladder cancer cell line EJ was treated with Rg3 of various concentrations. Cell proliferation was measured by MTT assay. Morphological changes of cells were observed by fluorescent staining of Hoechst 33258. Cell cycle and apoptosis rate were analyzed by flow cytometry (FCM). The expression of caspase-3 in cells was detected by immunocytochemistry. DNA ladder was showed by agarose gel electrophoresis.

RESULTRg3 inhibited proliferation of EJ cells in a manner of concentration-dependent relationship, IC50 of Rg3 in 48 h treatment was 125.5 mg x L(-1) to EJ cells. When treated with 150 mg x L(-1) of Rg3 for 24 h and 48 h, the cells showed apoptotic morphological characteristics including the condensed chromatin, the nuclear fragmentation, the apoptotic body and bright fluorescent granules as well as a higher caspase-3 expression. FCM assay indicated that Rg3 regulated cell cycle and induced apoptosis of EJ cells. When treated for 24 h and 48 h with 75 mg x L(-1) of Rg3 as well as for 48 h with 150 mg x L(-1) of Rg3, the percentages of cells in S phase and G2/M phase were increased, whereas the percentage of cells in G0-G1 was decreased. The apoptosis rates were increased from (1.05 +/- 0.17)% in control group cells to (8.41 +/- 0.98)%, (18.57 +/- 2.20)% and (33.98 +/- 1.64)%, respectively. Remarkable DNA ladders were revealed. The effects showed a manner in dose and time dependent of Rg3.

CONCLUSIONThe results suggest that ginsenoside Rg3 exerts an inhibiting effect on proliferation of EJ cells by inducing apoptosis.

Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Transitional Cell ; genetics ; metabolism ; pathology ; Caspase 3 ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA, Neoplasm ; genetics ; Dose-Response Relationship, Drug ; Electrophoresis, Agar Gel ; Flow Cytometry ; Ginsenosides ; administration & dosage ; isolation & purification ; pharmacology ; Humans ; Immunohistochemistry ; Inhibitory Concentration 50 ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Urinary Bladder Neoplasms ; genetics ; metabolism ; pathology

OBJECTIVETo observe the effect on P170, LRP, TOPO II of S180 tumour MDR mice for matter by 70% ethanol with Huanglian Jiedu Tang, and then discuss the molecular biology base for clinic.

METHOD18-22 gramme mice were divided into four groups for normal S180 tumour cell group, matter by 70% ethanol with Huanglian Jiede Tang 100 mg x kg(-1) and 50 mg x kg(-1) in random. Each mouse was given S180 cell 0.2 mL by celiac, and after 24 hours give cisplatin for Injective 3 mg x kg(-1), ip, once a week. And give cyclophosphamide and 5-FU 3 mg x kg(-1), ig, once every day. After 15 days, collect lively mice ascites and give it for onefold normal mice. And then repeat before process. At the same time, every group was given corresponding medicine for 0.2 mL x 10 g(-1). The normal group and the model group were given the same cubage water, all together fore weeks. At last observd the P170, LRP, TOPO II by flow cytometry.

RESULTMatter by 70% ethanol with Huanglian Jiedu Tang could obviously reduce the express of P170 and LRP, and the activiation of TOPO II.

CONCLUSIONMatter by 70% ethanol with Huanglian Jiedu Tang can intervene the ocurrence of the multi-drug resistance of tumour cells by regulating the biology gene.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Cell Line, Tumor ; Coptis ; chemistry ; DNA Topoisomerases, Type II ; metabolism ; Drug Combinations ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Ethanol ; chemistry ; Flow Cytometry ; Mice ; Phytotherapy ; Plants, Medicinal ; chemistry ; Sarcoma 180 ; metabolism ; pathology ; prevention & control ; Vault Ribonucleoprotein Particles ; metabolism

Animals ; Annexin A2 ; chemistry ; genetics ; metabolism ; physiology ; DNA Replication ; Endocytosis ; Exocytosis ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms ; metabolism ; pathology ; Prognosis ; Tissue Plasminogen Activator ; metabolism ; physiology