Tanshinone IIA: New Perspective on the Anti-Tumor Mechanism of A Traditional Natural Medicine.

The search for natural and efficacious antineoplastic drugs, with minimal toxicity and side effects, is an important part of antitumor drug research and development. Tanshinone IIA is the most evaluated lipophilic active component of Salvia miltiorrhiza. Tanshinone IIA is a path-breaking traditional drug applied in cardiovascular treatment. It has also been found that tanshinone IIA plays an important role in the digestive, respiratory and circulatory systems, as well as in other tumor diseases. Tanshinone IIA significantly inhibits the proliferation of several types of tumors, blocks the cell cycle, induces apoptosis and autophagic death, in addition to inhibiting cell migration and invasion. Among these, the regulation of tumor-cell apoptosis signaling pathways is the key breakthrough point in several modes of antitumor therapy. The PI3K/AKT/MTOR signaling pathway and the JNK pathway are the key pathways for tanshinone IIA to induce tumor cell apoptosis. In addition to glycolysis, reactive oxygen species and signal transduction all play an active role with the participation of tanshinone IIA. Endogenous apoptosis is considered the main mechanism of tumor apoptosis induced by tanshinone IIA. Multiple pathways and targets play a role in the process of endogenous apoptosis. Tanshinone IIA can protect chemotherapy drugs, which is mainly reflected in the protection of the side effects of chemotherapy drugs, such as neurotoxicity and inhibition of the hematopoietic system. Tanshinone IIA also has a certain regulatory effect on tumor angiogenesis, which is mainly manifested in the control of hypoxia. Our findings indicated that tanshinone IIA is an effective treatment agent in the cardiovascular field and plays a significant role in antitumor therapeutics. This paper reviews the pharmacological potential and inhibitory effect of tanshinone IIA on cancer. It is greatly anticipated that tanshinone IIA will be employed as an adjuvant in the treatment of various cancers.

The Mechanism of Quercetin in the Treatment of Lung Squamous Cell Carcinoma Based on a Protein-Protein Interaction Network.

Background: Lung squamous cell carcinoma (LUSC) is characterized by poor prognosis and obvious limitations of therapeutic methods. The molecular target and mechanism of quercetin (QR), a natural anticancer product with extensive pharmacological activities, on lung squamous cell carcinoma is still unclear. Method: The effects of QR on LUSC were examined using cell proliferation, migration, and invasion tests. Key target genes were screened using The Cancer Genome Atlas (TCGA) database, Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) database, STRING website, topology, and prognosis analysis, molecular docking, and other bioinformatics methods for further analysis. Finally, the effects of QR on the expression of key targets in LUSC cells were detected using a cell cycle assay and western blotting. Results: Our study demonstrates that QR not only inhibits the proliferation of LUSC but also affects the invasion and metastasis of LUSC. After downloading and analyzing the TCGA database, 2150 differentially expressed genes were identified. PLK1, CDC20, and BUB1B were identified using enrichment analysis, topological network analysis, cluster analysis, and molecular docking screening. Subsequent experiments showed that QR could interfere with the cell cycle and downregulate the expression of the target gene PLK1 at the protein level. Conclusions: We found that QR not only inhibits the proliferation, migration, and invasion but also blocks the cell cycle progression of LUSC. QR downregulated the expression of the LUSC target gene PLK1 at the protein level.

Production of myo-inositol from glucose by a novel trienzymatic cascade of polyphosphate glucokinase, inositol 1-phosphate synthase and inositol monophosphatase.

Myo-inositol (inositol) is important in the cosmetics, pharmaceutical and functional food industries. Here, we report a novel pathway to produce inositol from glucose by a trienzymatic cascade system involving polyphosphate glucokinase (PPGK), inositol 1-phosphate synthase (IPS) and inositol monophosphatase (IMP). The system contained three highly active enzymes, AspPPGK from Arthrobacter sp. OY3WO11, TbIPS from Trypanosoma brucei TREU927, and EcIMP from Escherichia coli. A trienzymatic cascade reaction was implemented, and the conversion ratio from glucose to inositol reached 90%, which is promising for the enzymatic synthesis of inositol without ATP supplementation.

[Prostatic urethral lift: A novel minimally invasive treatment for benign prostatic hyperplasia].

Benign prostatic hyperplasia (BPH) and BPH-induced lower urinary tract symptoms (LUTS) are common factors influencing the quality of life (QOL) of elderly males. In case of undesirable or adverse effects of medication, many BPH patients seek surgical treatment. Transurethral resection of the prostate (TURP), though evidently effective for BPH, fails to preserve the sexual function and therefore reduces the QOL of the patients. Moreover, some elderly patients with comorbidities may be unfit for TURP. Prostatic urethral lift (PUL) is a newly developed surgical procedure for the treatment of LUTS secondary to BPH. With the advantages of minimal invasiveness, low rate of peri- and post-operative complications, and maximal preservation of patients' erectile and ejaculatory functions, PUL is winning more and more attention from the clinicians and patients.

[Explorative study on mechanism and drug intervention for chronic allograft nephropathy induced by renal ischemia-reperfusion injury].

OBJECTIVE: This study is aiming to investigate the mechanism and drug intervention of chronic allograft nephropathy (CAN) induced by renal ischemia-reperfusion injury. METHODS: The closed colony strain Sprague-Dawley (SD) and Wistar Rats were used as donor and recipient, respectively. Orthotopic kidney transplantation was performed following the procedure of our previous study. The rats were divided into five groups: Group A only received CsA with 10 mg/(kg x d); except CsA, Group B,C,D received Yi Sheng injection with 4 mg/(kg x d), 8 mg/(kg x d), and MMF (20 mg/(kg x d)], respectively. Group E was control group. According to Banff standard, the serum creatinine (SCr) level and pathological change of rat grafted kidney were observed at the 4th, 8th and 12th weeks post-transplantation. The immunohistochemistry and real-time fluorescence quantitative polymerase chain reaction were used to comprehend the localization and expression of TGFbeta1 and Smad2, 7 in the transplant kidney. RESULTS: Compared with the lower dosage group, the differences of SCr level and pathological changes of CAN at all the time points after 8th week were statistically significant in the high dosage Yi Sheng group. It was showed that the Yi Sheng injection had the protective effect on CAN with a dose-dependent fashion. After transplantation, the rat kidney-sclerosis model showed that the up-regulated expressions of TGF-P, and Smad2 and the down-regulated expression of Smad7 in Group A and Group B were statistically significant, which meant that the difference was obvious when Group A compared with the other 4 groups. The expressions of TGF-beta1, and Smad2 were strongly positive in tubular epithelial cell, interstitial cell and glomerulus, while the expression of Smad7 was weak. Thickening of endovascular could significantly be inhibited in high dosage of Yi Sheng and MMF group. CONCLUSION: The up-regulated expressions of TGF-beta1 and Smad2 and the down-regulated expression of Smad7 may accelerate the progression of CAN alone or with immune factors. The traditional Chinese medicine Yi Sheng injection and MMF can down-regulate the expression of TGF-beta1 and Smad2 and block the down-regulated expression of Smad7, which may postpone and lessen the progression of CAN.

[Effects of heating on the epithelia of benign prostate hyperplasia in vitro].

OBJECTIVE: To investigate the biological changes of the epithelia of benign prostate hyperplasia under heating at different temperatures and at different points of time after heating. METHODS: Cell morphology, MTT, flow cytometer, and the immunocytochemical method for detecting heat shock protein 70 and prostate specific antigen were used to observe the effect of heating on the primarily cultured epithelia of benign prostate hyperplasia at 45 degrees C and 60 degrees C and at 1 hour and 12 hours after heating. RESULTS: Heating at 45 degrees C for 15 min resulted in apoptosis, and at 60 degrees C, necrosis in most of the cells. The inhibiting effect of heating on the growth of cells was observed, more significant in the 60 degrees C group than in the 45 degrees C group. The cell phase arrest induced by heat, mainly G0/G1 arrest, was more significant in the 12 h group than in the 1 h group. Heating up-regulated the expressions of heat shock protein 70 and prostate specific antigen in cells. CONCLUSION: Heating can induce apoptosis, necrosis and growth suppression of the epithelia of benign prostate hyperplasia. Its process and mechanism are correlated with the cell phase arrest and the up-regulation of the expressions of heat shock protein 70 and prostate specific antigen.

[The synergistic effects of docetaxol and retinoic acid on prostate cancer cell line PC-3].

OBJECTIVE: To observe the synergistic effects of docetaxol and retinoic acid on prostate cancer cell line PC-3 in vitro and in vivo. METHODS: Cell morphology, MTT, flow cytometry, immunocytochemical method were used to observe the effects of 10(-6) mol/L, 10(-7) mol/L, 10(-8) mol/L docetaxol and 10(-5) mol/L, 10(-6) mol/L, 10(-7) mol/L retinoic acid on prostate cancer cell line PC-3 in single or synergistic administration ways for 24 and 48 hours in vitro. Male BALB/C-nu mice with PC-3 prostate cancer cell lines were treated by docetaxol and retinoic acid singly or synergistically in vivo. Serum PSA of mice, weights of mice and PSA expression in xenograft tumors of mice by immunohistochemical method were measured. RESULTS: Above 10(-6) mol/L retinoic acid enhanced the growth suppression (suppression ratio > or = 69.2%, P<0.01), apoptosis (Apoptosis ratio > or = 23.8%, P<0.05) and down-regulation of the expression of cyclin D1 (expression ratio < or = 14.2%, P<0.05) induced by above 10(-7) mol/L docetaxol in PC-3 cells. Retinoic acid changed the ratio of G2/M phase induced by docetaxol from 70.3% to 54.6%, and reversed the G2/M arrest partially (P<0.05). Mean serum PSA of mice [(43+/-11) ng/ml], weight of xenograft tumors [(2.8+/-0.4) g] and PSA expression in tumors [(26+/-3.2)%] with PC-3 prostate cancer cell lines of nude mice were decreased significantly in docetaxol combined with retinoic acid group than in control group except weight of mice [(20.3+/-1.1) g]. CONCLUSION: Retinoic acid can enhance the growth suppression and apoptosis induced by docetaxol in synergistic way in vitro and in vivo, thus showing their great potential in the treatment of androgen-independent carcinoma of prostate.

[Clinical study on application of bailing capsule after renal transplantation].

OBJECTIVE: To observe and assess the immunosuppressive effect of applying bailing capsule (BLC, a dry powder preparation of Cordyceps sinensis mycelia), after renal transplantation, its influence on other systems of organism, and to explore the possible therapeutic mechanism. METHODS: One hundred and twenty-one recipients of renal homo-allograft were randomly divided into two groups. The 64 cases in Group A was treated with cyclosporin A (Cs A) + prednisone (pred) + azathioprine (Aza), the 57 in Group B treated with Cs A + pred + BLC. They were followed-up for 1-2 year by checking up blood routine, urine routine, liver and renal function, blood electrolytes, glucose and lipids, and uric acid for 2 times every week in the first month after transplantation, followed by proper re-examination of these items according to various condition. RESULTS: There was no significant difference between the two groups in aspects of graft survival rate, occurrence of reject reaction, renal function recovery, blood electrolytes and blood glucose levels. However, as compared with Group A, in Group B, levels of urinary erythrocytes and leucocytes, blood alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol, uric acid as well as the incidence of infection were significantly lower, and blood high density lipoprotein, serum total protein, albumin, RBC and WBC count were significantly higher. CONCLUSION: BLC could effectively prevent the reject response after renal transplantation, protect renal and liver function, stimulate hemopoietic function, improve hypoproteinemia and hyperlipidemia, reduce the infection, etc., therefore, it is an ideal immunosuppressor after organ transplantation.

[The effect of curcumin on bladder cancer cell line EJ in vitro].

OBJECTIVE: To observe the effect of curcumin on bladder cancer cell line EJ in vitro. METHODS: Cell morphology, MTT, flow cytometer, immunocytochemical method for detecting NF-KB, Cyclin D1 were used to observe the effect of 5,10,20 mg/L curcumin on bladder cancer cell line EJ in vitro. RESULTS: All concentrations curcumin resulted in the growth suppression significantly [Suppression ratio > or = (27.5 + 3.1)%, P < 0.05]. Above 10 mg/L concentrations curcumin induced apoptosis [Apoptosis ratio > or = (14.6 +/- 1.8)%, P < 0.05] and down-regulated of the expression of NF-kappaB [Expression ratio < or = (35.8 +/- 4.2)%, P < 0.05], Cyclin D1 [Expression ratio < or = (29.7 +/- 3.2)%, P < 0.05]. The cell phase arrest induced by curcumin was G1 phase arrest mainly with significant decrease of S phase. CONCLUSIONS: Curcumin can suppress the growth, induce apoptosis of bladder cancer EJ cell in vitro. Its mechanism is related with down-regulations of the expressions of NF-kappaB and Cyclin D1. Curcumin has great potential for the treatment of bladder cancer.